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At least 19 recordsLinked to original sources

PubMed1991

Serotonin inhibits the peptide FMRFamide response through a cyclic AMP-independent pathway in Aplysia.

1. The S-K+ conductance was isolated by voltage-clamping near the resting potential pleural mechanosensory neurons of Aplysia in culture. This background conductance is modulated in opposite directions by two distinct, transmitter-controlled second-messenger cascades: it is enhanced by the peptide FMRFamide through the 12-lipoxygenase pathway of arachidonic acid, and it is decreased by serotonin (5-HT) through adenosine 3',5'-cyclic monophosphate (cAMP)-dependent phosphorylation. 2. The dose-dependent activating effect of FMRFamide (0.01-500 microM) on the S-K+ conductance was measured in the presence and the absence either of 1-100 microM 8-bromo-cAMP (8b-cAMP, a membrane-permeable and hydrolysis-resistant analogue of cAMP), or of 0.01-0.1 microM 5-HT. 3. When 8b-cAMP was applied, it produced a slow inward current response due to closure of the S-K+ conductance. This response was antagonized by FMRFamide in a dose-dependent mode. Application of 100 microM FMRFamide, in the presence of 1-10 microM 8b-cAMP, produced an outward current response larger than the control FMRFa response and equal to the sum of the responses to FMRFamide alone and to 8b-cAMP alone. Similarly, at 500 microM, FMRFamide completely antagonized the closing action of maximal 8b-cAMP levels (100 microM). This observation confirms previous work that indicated that FMRFamide can reopen S-K+ channels closed by FMRFamide. 4. In contrast, in the presence of moderate concentrations of 5-HT (0.01 microM), which produce a slow inward current due to the closing of the S-K+ conductance, FMRFamide elicited a response that only partially antagonized this 5-HT action. Under maximal 5-HT concentrations (0.1 microM), the 5-HT response was not antagonized by any FMRFamide concentration: instead, the FMRFamide response was smaller than the control response without 5-HT. This experiment suggests that 5-HT, with an action independent from cAMP, inhibits the effect of FMRFamide on the S-K+ channel. 5. The dose-dependent inhibitory effect of 5-HT (0.001-10 microM) on the S-K+ conductance was measured in the presence and the absence either of FMRFamide (1-50 microM), which stimulates the release and metabolism of arachidonic acid in Aplysia sensory neurons or of arachidonic acid (25 microM). 6. Under these conditions, supramaximal concentrations of 5-HT could not completely suppress the slow outward current evoked by FMRFamide or by arachidonic acid, indicating that a component of the arachidonic-mediated response to FMRFamide is resistant to actions that maximally increase the S-K+ channel phosphorylation.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1991

Modulatory effects of serotonin, FMRFamide, and myomodulin on the duration of action potentials, excitability, and membrane currents in tail sensory neurons of Aplysia.

1. The electrophysiological properties of sensory neurons that mediate withdrawal reflexes of Aplysia can be modulated by a variety of neurotransmitters. We compared the known excitatory actions of serotonin (5-HT) with the actions of FMRFamide (Phe-Met-Arg-Phe-NH2) and myomodulin (Pro-Met-Ser-Met-Leu-Arg-Leu-NH2) on the durations of action potentials and excitability. In addition, with the use of voltage-clamp and pharmacological separation techniques, we characterized the membrane currents that were modulated by each of the three agents. 2. Application of 5-HT produced an increase in the duration of action potentials and an enhancement of excitability in somata of the tail sensory neurons. FMRFamide and myomodulin reversed these excitatory effects and decreased the duration of action potentials and excitability. These results indicated that FMRFamide and myomodulin exerted inhibitory effects on the electrophysiological properties of the sensory neurons. properties of the sensory neurons. 3. FMRFamide appeared to modulate three K+ currents. The first current, which was increased by FMRFamide, had properties closely resembling those of the S-K+ current (IK,S). These properties include slow activation, little inactivation, and relative insensitivity to the K+ channel blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA). The second current, which was reduced by FMRFamide, had kinetic and pharmacological properties similar to those of a component of the Ca(2+)-activated K+ current (IK,Ca). Finally, at large depolarizations, FMRFamide appeared to increase a third current that was attenuated by 4-AP, suggesting that FMRFamide also modulated the delayed or voltage-dependent K+ current (IK,V). 4. Myomodulin appeared to modulate two of the currents modulated by FMRFamide, because it increased both IK,S and IK,V. Unlike FMRFamide, however, myomodulin did not appear to modulate IK,Ca. 5. Arachidonic acid mimicked the modulation of IK,S, IK,Ca, and IK,V by FMRFamide. Because myomodulin did not modulate IK,Ca, it appears that a second messenger other than arachidonic acid or its metabolites mediates the modulatory effects of myomodulin. 6. These results indicate that both FMRFamide and myomodulin can inhibit the tail sensory neurons by increasing IK,S. FMRFamide, but not myomodulin, also reduces IK,Ca, which suggests that under some conditions FMRFamide may also have excitatory actions. Finally, these results suggest that the effects of FMRFamide and myomodulin may be mediated by different second-messenger systems.

4-Aminopyridine↗

PubMed1991

FMRFamide modulation of secretory machinery underlying presynaptic inhibition of synaptic transmission requires a pertussis toxin-sensitive G-protein.

The neuropeptide FMRFamide modulates synaptic transmission between identified neurons of the pond snail Helisoma trivolvis. FMRFamide causes a presynaptic inhibition of transmitter release by actions on ion channels and secretory machinery (Man-Son-Hing et al., 1989). The actions of FMRFamide on secretory machinery were studied using giant synapses that form between somata in culture. Using the calcium cage DM-nitrophen, synchronized, calcium-clamped release of neurotransmitter was promoted by UV photolysis. A series of UV flashes (15 msec duration) repeatedly promoted the transient synchronized release of neurotransmitter. Addition of FMRFamide reduced the magnitude of these flash-evoked inhibitory postsynaptic currents. Under conditions of synchronized transmitter release, FMRFamide modulates the secretory responsiveness to internal calcium. The release of neurotransmitter at somasoma synapses was determined to be quantal in nature. To test for the involvement of G-proteins in mediating the effects of FMRFamide on secretory machinery, the modulation of the frequency of miniature inhibitory postsynaptic currents (MIPSCs) was examined. Addition of FMRFamide reduced the frequency of MIPSCs without affecting intracellular free calcium measured with fura-2. Injection of a nonhydrolyzable analog of GTP, GTP gamma S, mimicked the effect of FMRFamide and reduced MIPSC frequency. Preinjection of the presynaptic soma with the A-protomer of pertussis toxin (PTX) prevented FMRFamide from reducing MIPSC frequency. Thus, a PTX-sensitive G-protein mediates the action of FMRFamide on secretory machinery. Similarly, preinjection of the presynaptic soma with PTX prevented FMRFamide from reducing the magnitude of action potential-evoked IPSC. Dose-response curves for the actions of FMRFamide on secretory machinery and calcium current were constructed and demonstrated that secretory machinery can be modulated at concentrations of FMRFamide (less than or equal to 10(-7) M) that do not affect calcium current magnitude. At a concentration of 10(-7) M FMRFamide, action potential-evoked synaptic transmission was reduced. Thus, synaptic transmission can be regulated by the modulation of secretory machinery, without a requirement for the modulation of ion channels.

Animals↗

PubMed1987

FMRFamide-like substances in the leech. III. Biochemical characterization and physiological effects.

FMRFamide-like immunoreactivity has been previously localized to identified neurons in the CNS of the leech, Hirudo medicinalis (Kuhlman et al., 1985a). These leech antigens have been characterized biochemically by reverse-phase high-pressure liquid chromatography (HPLC) followed by radioimmunoassay (RIA). The majority of the FMRFamide-like immunoreactivity recovered by HPLC from extracts of leech nerve cords coelutes with authentic FMRFamide. We have tentatively identified this major leech peptide as authentic FMRFamide. Two neurons that control heartbeat in the leech, the HE motor and HA modulatory neurons, and their neural processes on the heart are FMRFamide-like immunoreactive (Kuhlman et al., 1985a). Single individually dissected HE and HA cells were analyzed by HPLC and RIA. Only 1 FMRFamide-like peptide was found in extracts of HA cells; this peptide was chromatographically indistinguishable from authentic FMRFamide. The FMRFamide-like peptide in HE cells could not be isolated by experimental procedures used. Most of the FMRFamide-like immunoreactivity contained within the neural processes on the heart also coeluted with authentic FMRFamide. HE motor neurons, which are believed to be cholinergic (Wallace, 1981a, b; Maranto and Calabrese, 1984a, b), were examined for their FMRFamide-like effects on the heart. The presence of curare in the bathing medium did not block the ability of FMRFamide to induce myogenic activity in heart muscle, suggesting that FMRFamide and ACh act at different receptor sites on the heart. Prolonged firing in HE cells in the presence of curare also induced myogenic activity in heart muscle. This FMRFamide-like action of the HE motor neurons may be normally masked by their cholinergic actions.

Animals↗

PubMed1994

Characterization and solubilization of the FMRFamide receptor of squid.

The optic lobe of squid (Loligo pealei) contains FMRFamide receptors that can bind an iodinated FMRFamide analog: [125I]-desaminoTyr-Phe- norLeu-Arg-Phe-amide ([125I]-daYFnLRFa). Radioligand binding assays revealed that squid FMRFamide receptors are specific, saturable, high affinity sites (Kd = 0.15 nM) densely concentrated in optic lobe membranes (Bmax = 237 fmole/mg protein). The receptors appeared to be coupled to Gs because guanine nucleotides inhibit receptor binding and the stimulation of adenylate cyclase by FMRFamide is GTP-dependent. Both the binding and cyclase data showed that FMRFamide, but not FMRF-OH, interacts at FMRFamide receptors; thus the C-terminal Arg-Phe-amide is critical for binding. The high binding affinity of FMRFamide (0.4 nM IC50) was specific for FMRFamide-like peptides. The structure-activity relations of many FMRFamide analogs were defined in detail and were nearly identical for both the membrane-bound and detergent-solubilized receptors. We also found that squid optic lobe contains FMRFamide-like reactivity as measured with both a radioimmunoassay and a radioreceptor assay. Moreover, we have sequenced a fragment of genomic DNA that encodes a FMRFamide precursor. Our findings in sum suggest that FMRFamide is a neurotransmitter in squid optic lobe, and that this tissue is a good source from which to purify FMRFamide receptors.

Adenylyl Cyclases↗

PubMed1992

Supraspinal antinociception produced by [D-Met2]-FMRFamide in mice.

The ability of Phe-Met-Arg-Phe-NH2 (FMRFamide) or [D-Met2]-FMRFamide to produce antinociception in mice, or to block morphine-induced antinociception, was examined using the tail-flick and tail-immersion (55 degrees C) tests. [D-Met2]-FMRFamide dose-dependently produced antinociception following intracerebroventricular (i.c.v.) administration with ED50 values (95% confidence limits) of 5.0 (2.2-7.2) and 12.8 (8.1-19.9) micrograms in the tail-flick and tail-immersion tests, respectively. FMRFamide did not produce a maximal effect in the tail-flick test. Naloxone (administered s.c. 20 min prior to the i.c.v. administration of [D-Met2]-FMRFamide) dose-dependently attenuated [D-Met2]-FMRFamide-induced antinociception. The shift in the [D-Met2]-FMRFamide dose-response curve was parallel and a pA2 value for naloxone of 6.3 +/- 0.3 was determined from a Schild plot analysis. Mice made tolerant to the antinociceptive effect of morphine were cross-tolerant to the antinociceptive effect of [D-Met2]-FMRFamide. FMRFamide and [D-Met2]-FMRFamide both produced rightward, parallel shifts of the morphine antinociceptive dose-response curve. The findings that [D-Met2]-FMRFamide both elicited naloxone-sensitive antinociception and attenuated morphine-induced antinociception are consistent with the view that FMRFamide-related peptides (FaRPs) are weak agonists at opioid receptors and, further, appear to reconcile the apparently chimeric agonist and antagonist properties of these peptides observed in vivo.

Amino Acid Sequence↗

PubMed1992

FMRFamide effects on membrane properties of heart cells isolated from the leech, Hirudo medicinalis.

1. The effects of the cardioactive peptide FMRFamide were tested on enzymatically dissociated muscle cells isolated from hearts of the leech. These cells were normally quiescent, with resting potentials near -60 mV. 2. Superfusion of FMRFamide induced a strong depolarization in isolated heart cells (e.g., greater than 40 mV with 10(-6) M FMRFamide). The depolarization was maintained in the continued presence of peptide and persisted long after its removal. Less frequently, FMRFamide superfusion elicited an episodic polarization rhythm. 3. The response of isolated heart cells to bath-applied FMRFamide showed a 1- to 2-min latency. The latency decreased with repeated applications of FMRFamide. 4. The FMRFamide response was diminished by Na+ replacement but persisted with Ca2+ channel blockade. 5. In voltage-clamped heart cells (-60 mv), superfusion of FMRFamide elicited a slow inward current with a transient and a sustained component. 6. Current-voltage (I-V) curves during FMRFamide superfusion in normal leech saline showed that FMRFamide also enhanced voltage-dependent outward currents activated at depolarized levels. 7. Under conditions in which K+ currents were substantially blocked, the FMRFamide-dependent I-V curve was net inward from -90 to +50 mV. A voltage-dependent component was blocked by Co2+ and a linear component by Na+ replacement. 8. We conclude that FMRFamide elicits a persistent inward current with a Na+ component and in addition modulates both voltage-dependent Ca2+ and K+ currents that may contribute to the normal myogenic activity of leech heart muscle cells.

Animals↗

PubMed1991

SCPB-and FMRFamide-like immunoreactivities in lobster neurons: colocalization of distinct peptides or colabeling of the same peptide(s)?

Virtually all of the SCPB-like immunoreactive neurons (ca. 60 cells) in the lobster Homarus americanus also contain FMRFamide-like immunoreactivity. Control experiments reveal that SCPB-and FMRFamide-like immunoreactivities are successfully preadsorbed with their specific antigens, while the normal staining pattern is retained following preadsorption of each antibody with the alternate peptide. These experiments potentially lead to the conclusion that the anti-SCPB and anti-FMRFamide antibodies are labeling distinct compounds that are colocalized in lobster neurons. The lobster nervous system does not, however, contain authentic FMRFamide, but rather several FMRFamide-like compounds (Trimmer et al., J. Comp. Neurol. 266:16-26, 1987). The most abundant of these is the octapeptide TNRNFLRFamide. Experiments demonstrate that SCPB-like immunoreactivity is completely preadsorbed with synthetic TNRNFLRFamide, while there is a significant or complete loss of staining after preadsorption of the FMRFamide antibody with this molecule. Met-enkephalin-Arg-Phe-amide (YGGFMRFamide), an extended opioid peptide containing the FMRFamide sequence, also preadsorbs SCPB- and FMRFamide-like immunoreactivities, while Met-enkephalin-Arg-Phe (YGGFMRF) has no effect on the staining properties of these antibodies. These results suggest that the SCPB antibody can bind to extended forms of FMRFamide-like molecules, and that anti-SCPB and anti-FMRFamide antibodies may be colabeling one or more FMRFamide-like molecules in lobster neurons.

Amino Acid Sequence↗

PubMed1990

Distribution of FMRFamide-like immunoreactivity in the brain and suboesophageal ganglion of the sphinx moth Manduca sexta and colocalization with SCPB-, BPP-, and GABA-like immunoreactivity.

Using an antiserum against the tetrapeptide FMRFamide, we have studied the distribution of FMRFamide-like substances in the brain and suboesophageal ganglion of the sphinx moth Manduca sexta. More than 2000 neurons per hemisphere exhibit FMRFamide-like immunoreactivity. Most of these cells reside within the optic lobe. Particular types of FMRFamide-immunoreactive neurons can be identified. Among these are neurosecretory cells, putatively centrifugal neurons of the optic lobe, local interneurons of the antennal lobe, mushroom-body Kenyon cells, and small-field neurons of the central complex. In the suboesophageal ganglion, groups of ventral midline neurons exhibit FMRFamide-like immunoreactivity. Some of these cells have axons in the maxillary nerves and apparently give rise to FMRFamide-immunoreactive terminals in the sheath of the suboesophageal ganglion and the maxillary nerves. In local interneurons of the antennal lobe and a particular group of protocerebral neurons, FMRFamide-like immunoreactivity is colocalized with GABA-like immunoreactivity. This suggests that FMRFamide-like peptides may be cotransmitters of these putatively GABAergic interneurons. All FMRFamide-immunoreactive neurons are, furthermore, immunoreactive with an antiserum against bovine pancreatic polypeptide, and the vast majority is also immunoreactive with an antibody against the molluscan small cardioactive peptide SCPB. Therefore, it is possible that more than one peptide is localized within many FMRFamide-immunoreactive neurons. The results suggest that FMRFamide-related peptides are widespread within the nervous system of M. sexta and might function as neurohormones and neurotransmitters in a variety of neuronal cell types.

Animals↗

PubMed1986

Pharmacology of FMRFamide in Mytilus catch muscle.

In the anterior byssus retractor muscle (ABRM) of Mytilus, low concentrations of FMRFamide (10(-8)-10(-7) M) relax ACh-induced catch-tension, whereas high concentrations (greater than 10(-7) M) cause contraction. To study the structure-activity relations of these actions, a number of peptide analogs of FMRFamide were screened for their biological activities on the ABRM. The structure-activity relations for contraction were different from those for relaxation. Among the peptides tested, FMR-[D-Phe]-amide and gamma 1-MSH substantially antagonized FMRFamide contractions; but only gamma 1-MSH was even slightly antagonistic to FMRFamide-induced relaxation. Relaxations produced by 10(-7) M FMRFamide, or by 10(-5) M FMRFamide-relating relaxing peptides, were markedly depressed by treating the muscle first with 10(-5) M FMRFamide or with 10(-5) M FMRFamide-related contractile peptides. However, contractile agents that are structurally unrelated to FMRFamide, such as 3 X 10(-5) M SCPB and 2 X 10(-2) M caffeine, showed little or no such after-effect on the relaxation. Relaxations in response to submaximal serotonin, dopamine and repetitive electrical pulses of stimulation were not affected by a pretreatment with 10(-5) M FMRFamide. These results suggest that the ABRM of Mytilus has at least two pharmacologically distinct classes of receptors which are capable of being activated by FMRFamide.

Acetylcholine↗

PubMed1989

[The gating mechanism of K(+)-channels coupled to the FMRFamide receptor in the ganglion cells of Aplysia].

1. Neurons with a receptor responded to FMRFamide (Phe-Met-Arg-Phe-NH2) were identified in the ganglion of Aplysia kurodai. Ionic mechanism and channel gating system of the FMRFamide-induced responses were investigated by current clamp and voltage clamp methods. 2. The reversal potential of FMRFamide-induced response exactly coincided with the equilibrium potential for K+. This proved that the response was produced by a specific increase in membrane permeability toward K+, exclusively. 3. The FMRFamide-induced response was not affected by the inhibitors for Ca2(+)-activated K(+)-current, i.e., TEA, apamin, and EGTA. This excluded a possibility that FMRFamide-activated K(+)-channel is a Ca2(+)-activated K(+)-channel. 4. Intracellular injection of pertussis-toxin (PTX) caused no change in either resting potential or conductance, but it irreversibly blocked the FMRFamide-induced outward current within 30 min. Similarly applied cholera toxin (CTX) showed no effect on the FMRF-amide response. 5. Intracellular application of guanosine 5'-0-(2-thiodiphosphate) (GDP beta S) caused no effect on either resting potential or conductance, but it blocked the FMRFamide-induced K(+)-current within 3 min. 6. Intracellular application of guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S) alone induced a slowly developing, irreversible outward current associated with an increase in membrane conductance. However, repetitive applications of FMRFamide immediately after the start of GTP gamma S application markedly facilitated the effect of GTP gamma S on the resting membrane. 7. Intracellular application of either adenylate cyclase inhibitor (3'-deoxyadenosine) or A-kinase inhibitor (H-8) did not affect the FMRFamide-induced response. 8. It was concluded that the FMRFamide-induced K(+)-current is mediated by PTX-sensitive GTP-binding protein Gi, Go or Gk. It was also suggested that the FMRFamide-induced response is produced independently of the changes in intracellular Ca2+ or cyclic AMP.

Adenylate Cyclase Toxin↗

PubMed1987

The actions of FMRFamide-like peptides on visceral and somatic muscles of the snail Helix aspersa.

Phe-Met-Arg-Phe-NH2 (FMRFamide) and pyroGlu-Asp-Pro-Phe-Leu-Arg-Phe-NH2 (pQDPFLRFamide) occur in the ganglia and tissues of the snail, Helix aspersa. This report describes the effects of these two neuropeptides on five visceral organs or somatic muscles isolated from the snail (Table 1). The epiphallus, as well as the rest of the male reproductive tract, was contracted by both FMRFamide and pQDPFLRFamide, and the threshold was usually below 5 X 10(-9) mol l-1 (Fig. 1). Both peptides also reduced the resting tone of the crop and decreased the force and frequency of its rhythmic activity; FMRFamide is about 10 times more potent (Fig. 4). In contrast, pQDPFLRFamide was about 100 times more potent than FMRFamide as a cardioexcitatory agent (Fig. 5). The actions of the peptides on the pharyngeal and tentacle retractor muscles were markedly different: FMRFamide primarily contracted these muscles; and pQDPFLRFamide usually had no effect alone, but relaxed or diminished contractions induced by FMRFamide and acetylcholine (ACh) (Figs 6, 8, 9). Other analogues of FMRFamide were tested, but none was as effective a relaxing agent as pQDPFLRFamide. The effects of FMRFamide and pQDPFLRFamide on all of the preparations could be distinguished from those produced by ACh and 5-hydroxytryptamine (5-HT); thus the actions of the neuropeptides were not mediated by cholinergic or serotonergic neurones. The stimulation of the musculature in the male reproductive tract and the inhibition of motility of the digestive system by FMRFamide and pQDPFLRFamide implicate these peptides in the control of reproductive behaviour. The effectiveness of pQDPFLRFamide in relaxing the retractor muscles and as a cardioexcitatory agent led to the hypothesis that this heptapeptide and FMRFamide, acting at distinct receptors, cooperate to regulate the excitability and contractility of the snail's musculature between the extremes of aestivation and active locomotion.

Acetylcholine↗

PubMed1988

FMRFamide peptides in Helisoma: identification and physiological actions at a peripheral synapse.

Previous reports have demonstrated powerful neuromodulatory actions of the molluscan tetrapeptide FMRFamide in both the central and peripheral nervous systems of the freshwater snail Helisoma. The present study was designed to examine both the nature of the FMRFamide-like peptides in Helisoma and to define their physiological actions at a peripheral synapse. We report that, as determined by HPLC/RIA and mass spectrometry, Helisoma contains both FMRFamide and 2 of its analogs, FLRFamide and GDPFLRFamide. Whereas whole animals contain about 100 pmol/gm of these peptides, they were enriched in the nervous system (3000 pmol/gm) and in a peripheral target organ, the salivary glands (500 pmol/gm). For histochemical and physiological studies we examined the salivary glands, which are known to be innervated by neuron 4 of the buccal ganglion. We confirmed the presence of FMRFamide-like fibers on the salivary gland by immunohistochemistry using a polyclonal antiserum. These fibers appear to be largely derived from somata located in the central ring ganglia. For physiological tests we examined the neuron 4-gland synapse, at which presynaptic action potentials normally evoke a suprathreshold EPSP in gland cells. Bath application of FMRFamide, FLRFamide, or GDPFLRFamide at micromolar concentration to a buccal ganglia/salivary gland preparation completely suppressed spontaneous rhythmic activity. The sites of action of these peptides were examined by iontophoretic application of FMRFamide to neuron 4 or the salivary gland. Application of the peptide to the soma of neuron 4 caused a hyperpolarization that suppressed spontaneously generated action potentials. When applied to the salivary gland, FMRFamide caused a hyperpolarization that reduced the EPSPs evoked by neuron 4 to below spike threshold. The latter observation implies a postsynaptic locus of action for FMRFamide, and this possibility was tested by direct depolarization of the gland with iontophoresis of ACh (the putative transmitter of neuron 4). Such depolarizations were also reduced by FMRFamide. We conclude that Helisoma contains FMRFamide and 2 of its analogs, these peptides being enriched in the nervous system and salivary glands. Furthermore, these peptides can suppress activation of the salivary glands by actions both directly on gland cells and on the effector neuron.

Animals↗

PubMed1987

Identification of motor neurons that contain a FMRFamidelike peptide and the effects of FMRFamide on longitudinal muscle in the medicinal leech, Hirudo medicinalis.

Excitatory motor neurons in the leech are cholinergic. By using a combination of intracellular Lucifer yellow injection and indirect immunofluorescence, we localized FMRFamidelike immunoreactivity to a number of the motor neurons innervating longitudinal and dorsoventral muscle in the leech. All excitatory motor neurons innervating longitudinal muscle (cells 3, 4, 5, 6, 8, L, 106, 107, 108) were labeled with an antiserum to FMRFamide, while the inhibitory motor neurons innervating longitudinal muscle (cells, 1, 2, 7, 9, 102) were not. The excitatory motor neuron innervating medial dorsoventral muscle (cell 117) was labeled, while the excitatory motor neuron innervating lateral dorsoventral muscle (cell 109) was not. The inhibitory motor neuron innervating dorsoventral muscle (cell 101) was also labeled. Nerve terminals along dorsoventral muscle were also labeled with the antiserum. FMRFamide was bath applied to strips of longitudinal muscle while recording tension, and the muscle's response was compared to its response to the previously identified neuromuscular transmitter ACh. Brief applications of FMRFamide caused a contraction approximately one-tenth as large as that caused by an equimolar amount of ACh. The muscle response to FMRFamide was unaffected by curare. During extended exposures, FMRFamide caused a maintained contraction in longitudinal muscle without any apparent desensitization of the FMRFamide receptors and occasionally triggered an irregular myogenic rhythm. This extended exposure to FMRFamide caused a post-exposure potentiation of the longitudinal muscle's response to ACh that shorter applications of FMRFamide did not. Thus FMRFamide may act as a transmitter or modulator in cholinergic motor neurons innervating longitudinal and dorsoventral muscles in the leech.

Acetylcholine↗

PubMed1988

FMRFamide- and adipokinetic hormone-like immunoreactivity in the nervous system of the mosquito, Aedes aegypti.

As demonstrated with immunocytochemistry, specific cells and axons in the nervous system of female Aedes aegypti contain antigens immunologically related to FMRFamide (phenylalanine-methionine-arginine-phenylalanine-amide) and locust adipokinetic hormone I (AKH). In the supra-esophageal ganglion, including some medial neurosecretory cells, and in all ganglia of the ventral nerve cord, there are 100-120 cells immunoreactive to a FMRFamide antiserum. The same cells cross-react with a bovine pancreatic polypeptide antiserum, but when the latter antiserum is preabsorbed with FMRFamide, immunoreactivity is lost. However, immunoreactivity is maintained when FMRFamide antiserum is preabsorbed with pancreatic polypeptide, suggesting that the immunoreactive peptide is more closely related to FMRFamide. There are 6-12 cells in the supra- and subesophageal ganglia immunoreactive to an AKH antiserum, and some of the same cells are reactive to the FMRFamide antiserum. As well, unpaired cells in each of the abdominal ganglia are positive for both AKH and FMRFamide. Although the function of the FMRFamide- and AKH-like peptides in mosquitoes is unknown, this study, combined with previous reports on the localization of FMRFamide-like peptides in midgut endocrine cells, supports the concept of a brain-midgut neuroendocrine axis in this insect.

Aedes↗

PubMed1986

Gonadotropin-releasing hormone (GnRF), molluscan cardioexcitatory peptide (FMRFamide), enkephalin and related neuropeptides affect goldfish retinal ganglion cell activity.

Recently gonadotropin-releasing hormone (GnRF)-like and molluscan cardioexcitatory peptide (FMRFamide)-like compounds have been colocalized immunocytochemically to the terminal nerve, a presumed olfactoretinal efferent system in goldfish. In the present study these and related neuropeptides were shown to affect ganglion cell activity, recorded extracellularly, when applied to the isolated superfused goldfish retina. GnRF was usually excitatory. Salmon GnRF (sGnRF) was 10-30x more potent than chicken or mammalian GnRF. FMRFamide and enkephalin also were often excitatory but caused more varied responses than sGnRF. Met5-enkephalin-Arg6-Phe7-NH2 (YGGFMRFamide), which contains both enkephalin and FMRFamide sequences, tended to act like both of these peptides but with mainly enkephalin-like properties. Neuropeptide Y and the C-terminal hexapeptide of pancreatic polypeptides, whose C-terminus (-Arg-Tyr-NH2) is closely related to that of FMRFamide (-Arg-Phe-NH2), gave no consistent responses. Threshold doses were equivalent to: 0.1 microM for sGnRF; 0.5 microM for YGGFMRFamide; 1.5 microM for FMRFamide and enkephalin. Rapid, complete and irreversible desensitization was induced by single, 10-20x threshold doses of sGnRF; but desensitization was infrequent and limited with the other peptides. In general, all peptides tested affected the spatially and chromatically antagonistic receptive field components similarly, but selective actions were seen in a few cases with FMRFamide and with the opioid antagonist, naloxone. Responses, especially to sGnRF and FMRFamide, tended to be most frequently obtained and pronounced in winter and spring, suggesting a correlation with seasonally regulated sexual and reproductive activity. Our observations provide further evidence for transmitter-like roles of neuropeptides related to sGnRF and FMRFamide in the teleostean terminal nerve. The actions of agonists and antagonists, singly and in combination, imply strongly that there are distinctive postsynaptic receptors and/or neural pathways for GnRF-, FMRFamide- and enkephalin-like peptides in the goldfish retina.

Animals↗

PubMed1992

G-protein mediating the slow depolarization induced by FMRFamide in the ganglion cells of Aplysia.

Application of FMRFamide (Phe-Met-Arg-Phe-NH2) induced a slow depolarization in neurons of the Aplysia abdominal ganglion. In voltage-clamped cells, FMRFamide induced a slow inward current that increased when the membrane was depolarized beyond -85 mV, showing a negative slope conductance. However, this inward current never reversed to outward current when hyperpolarized beyond the equilibrium potential for K+. The FMRFamide-induced response was markedly augmented in Ca(2+)-free media, but depressed in Na(+)-free media. It was unaffected by a change in external potassium. Intracellular injection of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) significantly depressed the FMRFamide response in a dose-dependent way. Injection of cholera toxin (CTX) which did not cause any current response, selectively and irreversibly blocked the FMRFamide response. Neither 3'-deoxyadenosine, an inhibitor of adenylate cyclase, nor H-8, an inhibitor of cyclic adenosine 3',5'-monophosphate (cyclic AMP)-dependent kinase, depressed the FMRFamide response. 3-Isobutyl-1-methylxanthine (IBMX) did not augment the FMRFamide response appreciably. The FMRFamide response was not occluded at all by a relatively large injection of 8-bromo-cyclic AMP. It was concluded that the FMRFamide response is produced by the opening of the voltage-dependent Na(+)-channels via activation of a certain CTX-sensitive G-protein which is different from conventional "Gs" that activates adenylate cyclase.

1-Methyl-3-isobutylxanthine↗

PubMedDate not supplied

The action of FMRFamide (Phe-Met-Arg-Phe-NH2) and related peptides on mammals.

First purified 11 years ago from clam ganglia, FMRFamide (Phe-Met-Arg-Phe-NH2) was quickly demonstrated to be cardioactive in several molluscan species. Subsequent discovery that FMRFamide, or FMRFamide-related peptides (FaRPs), were present in mammalian central nervous system and gastrointestinal tract prompted investigations into the effect of FMRFamide on mammals. FMRFamide has now been shown to be cardioexcitatory in mammals, to inhibit morphine-induced antinociception, and to block morphine-, defeat-, and deprivation-induced feeding. It also inhibits colonic propulsive motility, induces behavioral effects when administered intrathecally, and has been reported to have amnesic effects in rodents. A proposal has arisen that a FMRFamide-like substance is an endogenous opioid antagonist and has stimulated a search for such a substance. However, FMRFamide has only weak affinity for opioid receptors and not all the actions of FMRFamide appear to be explained by actions at opioid receptors. Alternative mechanisms have been proposed which suggest that FMRFamide acts as a neuromodulator.

Animals↗