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G Simonnet

Publications and source records attributed to G Simonnet.

At least 37 records · Page 2Linked to original sources
PubMed1995

Neuropeptide FLFQRFamide receptors within the ventral mesenchephalon and dopaminergic terminal areas: localization and functional antiopioid involvement.

The neuropeptide FLFQPQRF amide is a FMRFamide-like peptide with some anti-opiate properties. Neuropeptide FLFQPQRFamide receptors are present in the mammalian central nervous system and have been clearly identified as different from opiate receptors. Autoradiography has revealed neuropeptide FLFQPQRFamide receptor localization within the ventral mesencephalon, where opiate receptors are also located. In order to delineate anatomical localization of neuropeptide FLFQPQRFamide receptors, we used selective chemical lesions of dopaminergic cells and intrinsic perikarya of the ventral mesencephalon, coupled with in vitro autoradiographic techniques. We show that: (i) unilateral lesions of dopaminergic perikarya produced by 6-hydroxydopamine did not affect either ipsi or contralateral neuropeptide FLFQPQRFamide receptor density within the mesencephalon; (ii) unilateral lesions of intrinsic perikarya by ibotenic acid injected into the ventral tegmental area produced a significant reduction of neuropeptide FLFQPQRFamide receptors (40%) in this region; (iii) in the substantia nigra pars compacta, ibotenic acid unilateral lesions did not affect the density of neuropeptide FLFQPQRF-amide receptors; (iv) unilateral 6-hydroxydopamine or ibotenic acid lesions failed to affect neuropeptide FLFQPQRFamide binding in the dopaminergic projection areas. These results suggest that, like opiate receptors, the neuropeptide FLFQPQRFamide binding sites are not localized on dopaminergic neurons but are distributed on both soma of non dopaminergic cells in the ventral tegmental area and on fibers afferent to the ventral tegmental area and substantia nigra pars compacta. To evaluate the possibility that the stimulation of neuropeptide FLFQPQRFamide receptors may affect the opioid modulation of mesocorticolimbic dopaminergic neuron activity, we tested the effects of neuropeptide FLFQPQRFamide ventral tegmental area infusion (0.25-10 micrograms) on the behavioral activation induced by intra-ventral tegmental area morphine infusion. We observed that in the ventral tegmental area, the stimulation of neuropeptide FLFQPQRFamide receptors inhibits morphine-induced locomotor hyperactivity. These results suggest that in the ventral tegmental area, neuropeptide FLFQPQRFamide may participate, via an indirect mechanism, to the control of the mesocorticolimbic dopaminergic system activity by counteracting the effect of opioids.

Animals↗
PubMed1995

Distribution of neuropeptide FF (FLFQPQRFamide) receptors in the adult rat spinal cord: effects of dorsal rhizotomy and neonatal capsaicin.

By using quantitative autoradiography and highly selective iodinated ligands, we quantified modifications in neuropeptide FF binding sites in the superficial layers (laminae I and II) of the cervical (C6-C8 segments) and lumbar (L3-L5 segments) enlargements in two models: (i) rats neonatally treated with capsaicin; (ii) rat submitted 15 days before to unilateral dorsal rhizotomies. We comparatively analysed the distribution of mu-opioid binding sites in the same animals. We have shown that the [125I]YLFQPQRFamide (neuropeptide FF sites) labelling is not significantly modified following selective damage of fine afferent fibres by neonatal capsaicin treatment. In the cervical and lumbar enlargements, capsaicin-treated/control binding ratios for [125I]YLFQPQRFamide were 0.90 and 0.86, respectively. While unilateral dorsal rhizotomy induced a drastic decrease in [125I]FK-33-824 labelling in the side ipsilateral to the lesion as compared to the intact side of (yielding ratios of 0.29 and 0.31 for cervical and lumbar levels, respectively), [125I]YLFQPQRFamide labelling was not significantly modified, yielding ratios of 0.98 and 0.91 for cervical and lumbar levels, respectively. These data suggest that, in contrast with a majority of mu-opioid receptors, neuropeptide FF receptors are not located on fine primary afferent fibers carrying nociceptive information from the fore- or hindlimb in the rat. This preferential postsynaptic localization, together with the reported "morphine modulating" action of this peptide, support the proposal of a role for neuropeptide FF in intraspinal modulation of nociceptive input.

Amino Acid Sequence↗
PubMed1995

Release of neuropeptide FF, an anti-opioid peptide, in rat spinal cord slices is voltage- and Ca(2+)-sensitive: possible involvement of P-type Ca2+ channels.

Neuropeptide FF (NPFF), an FMRFamide-like peptide with antiopioid properties, inhibits morphine-induced analgesia but also produces hyperalgesia. In the present study, the mechanisms of NPFF release were investigated in an in vitro superfusion system with rat spinal cord slices. The opening of voltage-sensitive Na+ channels with veratridine (20 microM) induced calcium-dependent NPFF release, which was abolished by tetrodotoxin (1 microM), suggesting that NPFF release depends on nerve impulse activity. We also showed that NPFF release was a function of the extent of depolarization and was calcium dependent. The 30 mM K(+)-induced release was blocked by Co2+ or Ni2+ (2.5 mM) but was unaffected by Ca2+ channel blockers of the L type--Cd2+ (100 microM), nifedipine or nimodipine (10 microM), diltiazem (20 microM), or verapamil (50 microM)--or the N type--omega-conotoxin GVIA (1 microM). In contrast, omega-agatoxin IVA (1 microM) led to a 65% reduction in NPFF release, suggesting that P-type Ca2+ channels play a prominent role. The 35% remaining release resulted from activation of an unknown subtype. The NPFF-like material in superfusates recognized spinal NPFF receptors, suggesting that NPFF release in the spinal cord has a physiological role.

Animals↗
PubMed1994

Modulation of neuropeptide FF release from rat spinal cord slices by glutamate. Involvement of NMDA receptors.

This study examined the effects of glutamate receptor agonists on the release of neuropeptide FF-like immunoreactivity from rat spinal dorsal half slices. Glutamate (10 microM) only induced release in Mg(2+)-free medium enriched with glycine (1 microM) and with slight depolarization (15 mM K+). This effect was abolished by the NMDA receptor antagonist, 2-amino-5-phosphonovalerate (100 microM), suggesting major participation of NMDA receptors. The quisqualate and metabotropic receptor agonists, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and trans-1-hydroxy-5-methylisoxazole-4-propionate (t-ACPD) respectively, had no effect at 10 microM. In contrast, NMDA dose dependently stimulated neuropeptide FF release, even in the presence of the Na+ channel blocker, tetrodotoxin (1 microM), suggesting that NMDA receptors involved in the release of neuropeptide FF are mainly located on nerve terminals. The NMDA receptor antagonists, 2-amino-5-phosphonovalerate or (+)-5-methyl-10-11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine (MK-801) (100 microM), blocked the 10 microM NMDA effect. Furthermore, neuropeptide FF-like material inhibited binding of [125I]Y8Fa, a radioiodinated analog of neuropeptide FF, to spinal membranes, suggesting physiological relevance of NMDA-induced release. Taken together, these results suggest a relationship between neuropeptide FF and NMDA receptors in the spinal cord.

2-Amino-5-phosphonovalerate↗
PubMed1994

Structure-activity study of neuropeptide FF: contribution of N-terminal regions to affinity and activity.

Twenty neuropeptide FF (NPFF) analogs having various lengths were synthesized by solid-phase peptide synthesis to gain more information on the role of N-terminal residues for the NPFF receptor affinity. The affinities were evaluated in the rat spinal cord membrane preparations, and the biological activities were measured on morphine analgesia in the mouse tail-flick test. Shortening of the NPFF sequence from the N-terminal produced only a moderate decrease in affinity until NPFF (4-8) was reached. In the same way, NPFF(3-8) significantly decreased morphine analgesia, while NPFF(4-8) had no significant effect at a dose of 22 nmol. The introduction in the N-terminal part of NPFF of a D-enantiomer at positions 2 and 1 or the presence of an N-methyl group on position 3 did not modify affinity and activity. Substitution of proline5 by the D-isomer decreased the affinity of NPFF analogs whatever their length, and [Tyr1,D-Pro5]NPFF(1-8) was 2.5-fold less potent than [Tyr1]NPFF(1-8) in reversing morphine-induced analgesia. In contrast, the presence of a glycine residue in position 5 did not influence the affinity toward NPFF receptors. Data provide evidence that the N-terminal segment of neuropeptide FF is responsible for high-affinity binding.

Amino Acid Sequence↗
PubMed1994

Autoradiographic localization of receptors for neuropeptide FF, FLFQPQRFamide, in human spinal sensory system.

The regional distribution of FLFQPQRFamide binding sites on fresh unfixed cryostate sections from post mortem specimens of human spinal cord and lower medulla oblongata was studied by quantitative autoradiographic methods using [125I]YLFQPQRFamide as ligand. Samples were taken from five cases who had died with no history of neurological disease at ages ranging from 5 months to 66 years. The biochemical and pharmacological characteristics of [125I]YLFQPQRFamide binding to mounted tissue sections were comparable to those reported for the rat in a previous study. [125I]YLFQPQRFamide appeared to interact reversibly with high affinity binding sites (Kd = 0.06 nM), distinct from opiate receptors. Sites labelled with [125I]YLFQPQRFamide were distributed unevenly within the human spinal cord and lower medulla oblongata, with the highest density in the superficial layers of the dorsal horn and the spinal trigeminal nucleus. Although moderate labelling was observed in the ventral part of spinal grey matter, dense labelling appeared in the gracile and cuneate nuclei. No binding sites were detected in white matter. These results show that, as in the rat, FLFQPQRFamide receptors in the human spinal cord and lower medulla oblongata, are mainly concentrated within spinal areas implicated in the analgesic action of opiates. The possible role of these receptors in modulating spinal nociceptive information is discussed with respect to the pharmacological effects of substances acting on FLFQPQRFamide receptors in animals.

Aged↗
PubMed1994

Characterization of a potent agonist for NPFF receptors: binding study on rat spinal cord membranes.

Specific receptors for the octapeptide FLFQPQRFamide (NPFF), a mammalian FMRFamide-like neuropeptide with anti-opiate properties have been identified in rat central nervous system. However, exploration of the biological role of this peptide requires a peptidase-resistant agonist. In this study, the stability and binding characteristics of [125I]DYLMeFQPQRFamide, a radioiodinated analogue of NPFF, on rat spinal cord tissue were determined and compared with those of [125I]YLFQPQRFamide, the reference ligand which previously permitted to characterize NPFF binding sites. In a binding assay, [125I]DYLMeFQPQRFamide remained intact in the presence of membranes without peptidase inhibitors, whereas [125I]YLFQPQRFamide was completely hydrolysed. The specific binding was time-dependent, dose-dependent, saturable and reversible. [125I]DYLMeFQPQRFamide shared the same binding characteristics as [125I]YLFQPQRFamide (Kd = 0.07 nM; Bmax = 14.7 fmol/mg protein). Binding was not affected by various spinal cord opioids or peptides. Autoradiographic studies indicated that binding sites were mainly located in the most external layers of dorsal horn where high densities of NPFF binding sites have previously been described. [125I]YLFQPQRFamide and [125I]DYLMeFQPQRFamide binding sites were both GTP-regulated. These findings indicate that DYLMeFQPQRFamide should be of value in studies on NPFF-mediated actions in vivo.

Amino Acid Sequence↗
PubMed1993

Characterization of a morphine-modulating peptide, FLFQPQRFamide, in the rat hypophysis: biochemical and immunocytochemical studies.

The octapeptide FLFQPQRFamide (F8Fa) is a FMRFamide-like peptide with a certain number of antiopiate properties. Previous studies have shown that both F8Fa specific receptors and F8Fa-like material are present in the rat central nervous system. In this study, RIA revealed that the rat neurohypophysis also contains F8Fa immunoreactive (IR) material (230 +/- 49 pg/neural lobe). HPLC profiles revealed several forms of F8Fa IR. Neurohypophysis extracts can also inhibit the binding of F8Fa to rat spinal cord preparations, which suggests that this F8Fa-like material has a biological activity. Immunocytochemical observations, at the light and electron microscopic levels, confirmed the presence throughout the neural lobe of F8Fa IR, in axonal fibers and terminals similar to those containing the more classical neurohypophysial hormones. Immunogold staining showed that F8Fa IR was restricted to neurosecretory granules in certain axonal and terminal profiles. Double staining of the same ultrathin sections, using our anti-F8Fa antiserum and vasopressin or its neurophysin specific antibodies, revealed that F8Fa IR was colocalized with vasopressin. F8Fa IR was not visible in ocytocinergic fibers or terminals. A striking depletion of F8Fa IR (80%) was observed in rats which were given 2% saline to drink for 6 days. Similarly, an ip injection of an hypertonic saline solution was shortly followed by a 20% drop of F8Fa IR. In vitro F8Fa IR release from isolated neurohypophysis was evoked under a 56 mM KCl depolarization. These results suggest that F8Fa IR may act as a paracrine/endocrine mediator released from the rat neurohypophysis.

Amino Acid Sequence↗
PubMed1992

Analogues of F8Famide resistant to degradation, with high affinity and in vivo effects.

Four analogues of Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2, a mammalian FMRFamide-like peptide with antiopiate properties, were synthesized with N-terminus modifications and were shown to have high affinity for F8Famide binding sites. The degradation rate of these analogues in mouse brain slices was 3 times lower than that of the natural peptide. One analogue, (2DME)Y8Fa (D.Tyr-D.Leu-[N-Me]Phe-Gln-Pro-Gln-Arg-Phe-NH2), produced a clear hyperalgic effect and inhibited morphine analgesia in the mouse tail-flick test at lower doses than did the parent compound. (3D)Y8Fa (D.Tyr-D.Leu-D.Phe-Gln-Pro-Gln-Arg-Phe-NH2) and (2D)Y8Fa (D.Tyr-D.Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) in contrast did not decrease morphine analgesia but were analgesic alone. The analgesic effects of 22 nmol (2D)Y8Fa and (3D)Y8Fa were decreased by (1DME)Y8Fa (D.Tyr-Leu-[N-Me]Phe-Gln-Pro-Gln-Arg-Phe-NH2) or (2DME)Y8Fa and were reversed by naloxone. These results indicate opioid modulating properties of F8Famide. These analogues may prove to be useful tools for studying the modulation of pain by F8Famide.

Amino Acid Sequence↗
PubMed1992

[Spontaneous splenic rupture disclosing a pheochromocytoma].

Clinical manifestation of a phaeochromocytoma may range from no symptoms to an acute abdominal emergency. These abdominal emergencies are related to haemorrhagic necrosis of the tumour, or massive bleeding in the retroperitoneal space. The authors report a case of splenic rupture revealing a phaeochromocytoma. The mechanism of splenic rupture is discussed as is the conservative treatment of phaeochromocytoma during splenic surgery. The authors observed no correlation between plasma catecholamine concentration and blood pressure.

Adrenal Gland Neoplasms↗
PubMed1992

Modulation of human lymphocyte proliferation by FLFQPQRFamide, a FMRFamide-like peptide with anti-opiate properties.

The octapeptide Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (F8Fa), originally detected in mammalian brain by antisera raised against the invertebrate peptide Phe-Met-Arg-Phe-NH2 (FMRFamide) is a neuropeptide able to antagonize the actions of both endogenous and exogenous opiates. Since it is well accepted that lymphocytes are targets for opiates, we have tested the effect of F8Fa on T cell proliferation from normal human peripheral blood lymphocytes. Our study shows that F8Fa exerts a concentration-dependent diphasic modulation of human T lymphocyte proliferation. Thus, despite a great variability between individuals, 10(-13) M F8Fa was found to enhance the proliferation of T cells induced by phytohemagglutinin or anti-CD2 monoclonal antibodies, while 10(-7) M F8Fa inhibited T cell proliferation, without affecting cell viability. When F8Fa was tested on monocyte-depleted cell preparations, only the inhibitory effect was observed. These results indicate that F8Fa may stimulate T cells via monocytes, but may also directly inhibit T lymphocyte proliferation. Given the presence of F8Fa-like peptide in human plasma, we suggest that F8Fa may act as a neurohormone in the control of the immune system.

Carbohydrate Sequence↗
PubMed1992

Autoradiographic distribution of receptors to FLFQPQRFamide, a morphine-modulating peptide, in rat central nervous system.

The neuropeptide FLFQPQRFamide is a structure related to FMRFamide which is able to inhibit the effects of both endogenous and exogenous opiates. This morphine-modulating activity is mediated via the stimulation of specific FLFQPQRFamide receptors, different from opiate receptors. In vitro quantitative receptor autoradiography was performed on frozen sections of rat central nervous system to characterize binding properties and visualize FLFQPQRFamide receptors using the specific ligand [125I]YLFQPQRFamide, a radio-iodinated analogue of FLFQPQRFamide. [125I]YLFQPQRFamide appeared to interact reversibly with a single class of binding sites (KD = 0.2 nM). The specific binding represented 80% of the total binding at 0.05 nM, the FLFQPQRFamide concentration used in this mapping study. Sites labelled with [125I]YLFQPQRFamide were distributed heterogeneously within the brain and spinal cord. A high density of FLFQPQRFamide binding sites was detected in the most external layers of the dorsal horn of spinal cord and various nuclei of pons and medulla including trigeminal, dorsal tegmental and reticular nuclei. Nucleus of solitary tract, parabrachial, ambiguous and facial nuclei are also intensively labelled. Some structures of mesencephalon and diencephalon exhibited a high density of FLFQPQRFamide binding sites: central gray, raphe nuclei and thalamic nuclei such as parafascicular, laterodorsal, central median, paratenial and paraventricular nuclei. Suprachiasmatic and mammillary nuclei, lateral, posterior and anterior areas of hypothalamus and medial preoptic area exhibited high labelling. FLFQPQRFamide binding sites were also seen in some structures of the dopaminergic meso-cortico-limbic system including ventral tegmental area, cingulate cortex, lateral septum and the head of the caudate-putamen. Dense labelling appeared in the presubiculum of hippocampus. The dissimilar mapping of FLFQPQRFamide and opiate brain receptors confirms our previous pharmacological findings in FLFQPQRFamide binding studies on rat spinal cord membranes, showing that FLFQPQRFamide receptors are different from opiate receptors. There was a good correspondence between localization of binding sites and that of the putative endogenous peptide. Both occur in brain areas previously associated with analgesic action of opiates. However, the mapping of FLFQPQRFamide receptors in the central nervous system suggests that the FLFQPQRFamide system could be implicated in other physiological functions.

Animals↗
PubMed1991

[Plasma catecholamines in brain death].

The purpose of this study was to find out whether a severe fall in plasma catecholamines levels can be observed in brain dead patients, that might contribute to haemodynamic disturbances in these patients. Plasma catecholamines (epinephrine and norepinephrine) were measured by HPLC combined with electrochemical detection in 18 consecutive brain dead patients referred to the multiorgan donors unit at the Bordeaux University Hospital. Two samples were obtained: the first one at the time of donor referral (11.2 +/- 9 h after the clinical onset of brain death), and the second one just before organ procurement (19.8 +/- 1 h after the clinical onset of brain death). The results showed that plasma catecholamines levels were similar in both samples, with mean values within the normal range. There was no correlation between the plasma levels of each of the catecholamines and the mean arterial pressures at the time of sampling. Very high plasma catecholamines levels have been found by other authors after brain injuries. After the onset of brain death, they return to basal rest values and do not continue to fall as is the case in animal experiments. The haemodynamic disturbances observed in brain dead patients therefore cannot be due only to sympathoadrenal failure.

Adult↗
PubMed1991

Characterization and localization of a putative morphine-modulating peptide, FLFQPQRFamide, in the rat spinal cord: biochemical and immunocytochemical studies.

The bovine octapeptide Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (FLFQPQRFamide), originally detected by antisera raised against the invertebrate peptide, Phe-Met-Arg-Phe-NH2, is a neuropeptide which antagonizes the actions of endogenous and exogenous opiates. Using a sensitive radioreceptor assay, we show that rat spinal cord extracts were able to inhibit binding of FLFQPQRFamide, suggesting that a biologically active FLFQPQRFamide-like material exists in the rat spinal cord. We also raised antibodies against the peptide and used them, together with radioimmunological and immunohistochemical methods, to characterize this material further and analyse its cellular and subcellular localization in this area of the central nervous system. Radioimmunoassay showed that extracts from cervical and thoracolumbar levels contained measurable amounts of FLFQPQRFamide-immunoreactive material (about 3 ng/g tissue), present essentially in the dorsal horn. Analytical reverse-phase chromatography revealed that this material existed in several molecular forms. One of these fractions (about 20% of the total immunoreactivity) had the elution characteristics of synthetic FLFQPQRFamide. Light microscopic immunohistochemistry showed FLFQPQRFamide immunoreactivity at all spinal levels, localized mainly in a dense plexus of fibers in the superficial layers of the dorsal horn. Immunoreactive profiles were also seen in the lateral funiculi and around the central canal at all levels and in the intermediolateral columns; some rare immunoreactive fibers were also noted in the ventral horn at cervical and thoracic levels. FLFQPQRFamide-positive cell bodies were never detected in any of our sections. Electron microscopy of ultrathin sections of the dorsal horn and central gray treated with our antisera and a post-embedding immunogold procedure revealed that the immunoreactivity, at least within these areas, was restricted to dense-cored vesicles (90-120 nm in diameter) in axonal and terminal profiles. As seen by radioimmunoassay and immunohistochemistry, unilateral rhizotomy of all dorsal roots between segments C4 and T2 did not change the levels of FLFQPQRFamide immunoreactivity in the ipsilateral C6-C8 segments. Taken together with our recent data showing the existence of specific FLFQPQRFamide receptors at the spinal cord level, our present observations suggest that the dorsal horn of the rat spinal cord may be a site where vertebrate Phe-Met-Arg-Phe-like peptides, and in particular, FLFQPQRFamide, may exert opiate modulating activities.

Animals↗
PubMed1990

Differential interactions of cholecystokinin and FLFQPQRF-NH2 with mu and delta opioid antinociception in the rat spinal cord.

An in vivo preparation of the rat spinal cord was used to investigate the electrophysiological actions of two non-opioid peptides, cholecystokinin (CCK8) and FLFQPQRF-NH2 (FMRFamide-like peptide) applied intrathecally. These compounds were examined alone and as a pretreatment before DAGO, a mu opioid agonist, and DSTBULET, a delta opioid agonist, both which selectively reduce C-fibre evoked dorsal horn neurone activity elicited by transcutaneous electrical stimulation. Given alone, CCK8 (1 microgram) elicited a modest enhancement of C-fibre induced activity which returned to control levels after 20 min, while FLFQPQRF-NH2 (10 micrograms) had no significant effect on C-fibre evoked firing. As a pretreatment, however, both peptides selectively prevented the inhibition of C-fibre evoked activity normally resulting from intrathecal DAGO, while having no effect on that resulting from DSTBULET. Further, CCK8 enhanced the facilitation of C-fibre evoked firing normally observed with low doses of DAGO. These data indicate that the anti-opioid roles suggested for CCK8 and FLFQPQRF-NH2 may be specific for neural elements utilizing the mu opioid receptor.

Animals↗
PubMed1989

Characterization of rat spinal cord receptors to FLFQPQRFamide, a mammalian morphine modulating peptide: a binding study.

An in vitro binding assay, using 125I-YLFQPQRFamide, a newly synthetized iodinated analog of FLFQPQRFamide, in which Phe1 (F) has been substituted by a Tyr (Y), was developed to demonstrate and characterize putative binding sites of this brain morphine modulating peptide. This radioligand bound in a time-dependent manner to rat spinal cord membrane preparation. This binding was dose-dependent, saturable and reversible. Both kinetic data and saturation measured at equilibrium lead to the existence of a homogenous population of high affinity binding sites with a Kd value of 0.09-0.1 nM and a maximal capacity Bmax of 14.5 +/- 2 fmol/mg protein. Results of competition experiments show that both FLFQPQRFamide and its analog YLFQPQRFamide had a similar capacity to inhibit the 125I-YLFQPQRFamide binding, suggesting that this radioiodinated analog is a good tool to study binding characteristics of FLFQPQRFamide receptors. The related octadecapeptide AGEGLSSPFWSLAAPQRFamide, another mammalian morphine modulating peptide competes for radioligand binding with similar potency. Our results also show that mu, delta and kappa opiate receptor agonists as well as the antagonist naloxone were not able to affect binding either in presence or in absence of 120 mM NaCl. Together, these data demonstrate that FLFQPQRFamide does not function as an endogenous opiate receptor antagonist and that is capacity to reduce opiate-induced analgesia is supported by specific binding sites.

Amino Acid Sequence↗
PubMed1989

Characteristics and specific localization of receptors for atrial natriuretic peptides at non-neuronal cells in cultured mouse spinal cord cells.

Characteristics of atrial natriuretic peptide receptors were determined in cultured mouse spinal cord cells. Saturation and competition experiments demonstrated the presence of a single class of atrial natriuretic peptide binding sites with high affinity (KD = 0.054 nM) and a density of 1.92 fmoles/10(6) cells. A similar affinity (KD = 0.070 nM) was observed in rat spinal cord membrane preparations. These atrial natriuretic peptide binding sites were functional receptors since the treatment of cells with atrial natriuretic peptide increased cyclic guanosine monophosphate levels within these cells in a classical time-dependent manner. When atrial natriuretic peptide was applied onto the cell body of intracellularly recorded spinal cord neurons, this peptide did not evoke a change of the input resistance or of the resting membrane potential value. Light-microscopic autoradiography studies showed that no atrial natriuretic peptide binding could be detected on typical birefringent neurons but it could be located on astroglial and epithelial cells as identified by immunocytochemical markers. These results show that functional atrial natriuretic peptide receptors with high affinity exist in cultured mouse spinal cord cells and are not located on neurons. The presence of atrial natriuretic peptide receptors on astrocytes suggests that this neuropeptide might be a good candidate for neuron-glial communication. As the atrial natriuretic peptide binding sites previously shown in epithelia responsible for maintaining fluid and electrolyte gradients, the atrial natriuretic peptide receptors on epithelial cells in these spinal cord cultures may be involved in vivo in the control of water balance in the central nervous system.

Animals↗