Biomedical subjects

H Vaudry

Publications and source records attributed to H Vaudry.

At least 361 records · Page 20Linked to original sources

PubMed1992

Pharmacological characterization of vasotocin stimulation of phosphoinositide turnover in frog adrenal gland.

In a previous report we demonstrated the presence of a vasotocin (AVT)-like peptide in chromaffin cells of the amphibian adrenal gland and showed that synthetic AVT is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical cells. In the present study we evaluated the relative potency of various AVT analogs and investigated the mechanism of action of AVT on frog interrenal (adrenal) tissue. Several AVT agonists, including hydrin 2, oxytocin (OXT), arginine vasopressin (AVP), Lys-conopressin G, and mesotocin (MT), were able to mimic the stimulatory effect of AVT on steroid secretion, but AVT was by far the most potent stimulator of steroidogenesis. In the series of analogs studied, the order of potency was: AVT greater than hydrin 2 greater than OXT greater than AVP greater than Lys-conopressin G greater than MT greater than [deamino-Cys1,D-Arg8]AVP greater than [d(CH2)5,Tyr(OMe)2] AVP. The effect of AVT (5 x 10(-10) M) was totally blocked by both the antidiuretic V2 antagonist [d(CH2)5,D-Phe2,Ile4,Ala9-NH2]AVP (10(-6) M) and the oxytocinergic antagonist [d(CH2)5,Tyr(OMe)2,Orn8]AVT (10(-6) M); the V2 antagonist was approximately twice as potent as the OXT antagonist. In contrast, the V1 antagonist 1-(1-mercapto-4-phenylcyclohexaneacetic acid)-AVP (10(-6) M) did not affect the response of the interrenal tissue to AVT. Indomethacin (5 microM), a cyclooxygenase inhibitor, induced a dramatic decrease in the spontaneous secretion of corticosteroids, but did not impair the stimulatory effect of AVT (5 x 10(-9) M) on corticosterone and aldosterone secretion. In addition, AVT did not stimulate the production of prostaglandin E2, suggesting that prostaglandins are not involved in the mechanism of action of AVT. Concurrently, AVT did not modify cAMP production by frog adrenal slices. In contrast, AVT induced both an increase in inositolphosphate production and a reduction of membrane phospholipid content. We conclude that in the frog adrenal gland, the stimulatory effect of AVT on steroid secretion is mediated through activation of receptors related to the mammalian V2 and/or OXT receptors, which are positively coupled to phosphoinositide-specific phospholipase C.

Adrenal Cortex Hormones↗

PubMed1992

Pituitary adenylate cyclase-activating polypeptide stimulates calcium mobilization in amphibian pituitary cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38-amino acid peptide of the glucagon-secretin-vasoactive intestinal polypeptide superfamily. Although PACAP is a potent stimulator of adenylate cyclase activity in the adenohypophysis, the precise target cells for PACAP in the anterior pituitary remain unknown. The aim of the present study was to investigate whether PACAP could stimulate calcium mobilization in individual cells of the pituitary and to determine the type of cells that responded to PACAP. Enzymatically dispersed frog distal pituitary cells were plated on photoetched coverslips and cultured for 3-7 days. The cells were loaded with the fluorescent calcium indicator indo-1, and changes in intracellular calcium concentrations ([Ca2+]i) were monitored using dual wavelength microfluorimetry. The individual cells were localized with the aid of the alpha/numeric grid of the coverslips and identified retrospectively by immunofluorescence. Approximately 45% of GH and PRL cells and 25% of ACTH and TSH cells responded to PACAP (10(-5) M) ejection by an elevation of [Ca2+]i. Only 16% of gonadotropes were stimulated by PACAP. The time course of [Ca2+]i variations showed three different patterns: transient spikes, sustained stimulations, and oscillatory responses. In addition, heterogenous responses were observed within each cell type. These data provide evidence for the involvement of calcium mobilization in the mechanism of action of PACAP on pituitary cells. The results also indicate that in frogs, PACAP may stimulate the secretory activity of GH and PRL cells and, to a lesser extent, ACTH, TSH, and gonadotrope cells.

Adrenocorticotropic Hormone↗

PubMed1992

Effect of vasotocin on cytosolic free calcium concentrations in frog adrenocortical cells in primary culture.

In a previous report we have shown that vasotocin (AVT), the amphibian counterpart of vasopressin, is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical cells. We have also observed that the stimulatory effect of AVT on corticosteroid secretion is mediated through activation of receptors positively coupled to phospholipase-C. In the present study we examined the effect of AVT on cytosolic Ca2+ concentrations ([Ca2+]i). Since the interrenal (adrenal) gland of the frog is composed of a mixed population of chromaffin and adrenocortical cells, cytochemical identification of cultured cells was performed by immunofluorescence, using antibodies to AVT or 11 beta-hydroxylase as markers of chromaffin cells or steroid-producing cells, respectively. Cultured interrenal cells were loaded with the fluorescent Ca2+ indicator indo-1, and variations in [Ca2+]i were studied using dual emission wavelength microfluorimetry. Exposure of adrenocortical cells to AVT induced elevation of [Ca2+]i. Prolonged infusion of AVT caused an immediate increase in [Ca2+]i, followed by a sustained response of adrenocortical cells. Repeated pulses of AVT resulted in a gradual decline in the [Ca2+]i increase, suggesting the existence of a desensitization phenomenon. The effect of AVT on calcium mobilization was totally blocked when the cells were incubated in the presence of the V2 antagonist [d(CH2)5,D-Phe2,Ile4,Ala9-NH2]AVP. In calcium-free medium, the AVT-evoked increase in [Ca2+]i was suppressed. In contrast, when Ca2+ was replaced by Mn2+ in the incubation medium, the early response of the cells (transient peak of [Ca2+]i) was preserved, while the plateau phase disappeared. Incubation of the cells with the dihydropyridine Ca2+ channel blocker nifedipine did not affect the AVT-induced [Ca2+]i rise. These results indicate that AVT exerts a dual action on [Ca2+]i in frog adrenocortical cells. The initial rise of [Ca2+]i can be ascribed to immediate mobilization of intracellular Ca2+ stores, probably mediated by inositol trisphosphategated channels, whereas the sustained increase in [Ca2+]i results from nifedipine-insensitive plasma membrane Ca2+ channels.

Adrenal Cortex↗

PubMed1992

Characterization of dopamine receptors associated with steroid secretion in frog adrenocortical cells.

We investigated the type of receptors involved in the mechanism of action of dopamine on corticosteroid secretion from the frog interrenal (adrenal) gland, using the in-vitro perifusion technique. Exposure of dispersed interrenal cells to 50 microM dopamine for 20 min had a biphasic effect on corticosterone and aldosterone secretion, i.e. a transient stimulation followed by an inhibitory phase. Repeated administration of equimolar pulses of dopamine, given at 150-min intervals, resulted in an enhancement of corticosteroid secretion followed by a subsequent blockade of the stimulatory phase of the response. In contrast, the dopamine-evoked inhibition of corticosteroid release did not show any sensitization or desensitization phenomena. Infusion of repeated pulses of the D1 receptor agonist SKF38393 (32 microM) stimulated corticosteroid release and mimicked the sensitization-desensitization phenomenon induced by dopamine. Repeated administration of the D2 receptor agonist LY171555 (50 microM) resulted in a reproducible inhibition of corticosterone and aldosterone secretion. These results suggested the presence of two different receptors for dopamine, i.e. D1 and D2, on frog adrenocortical cells, responsible respectively for the stimulatory and inhibitory effects of dopamine on steroid secretion. However, bromocriptine (50 microM) and CV205-502 (50 microM), two other D2 receptor agonists, had no effect on corticosteroid release. In addition, several classical D2 receptor antagonists failed to block the effect of dopamine on steroidogenesis. It was also observed that (-)sulpiride, a specific D2 antagonist, did not alter dopamine-induced inhibition of inositol phosphate formation. On the other hand, dopamine and the selective D1 and D2 antagonists SKF38393 and LY171555 did not affect the formation of cyclic AMP by interrenal tissue. Taken together, these data indicate that dopamine directly regulates corticosteroid secretion from frog adrenocortical cells. The effect of dopamine is not coupled to adenylate cyclase activity but is probably mediated through the phosphoinositide-turnover pathway. The pharmacological characteristics of the receptors involved in the mechanism of action of dopamine clearly differ from those of the D1 and D2 subtypes previously described in mammals.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1992

Glucocorticoids, transmitters and stress.

Many kinds of stress stimulate the neuroendocrine systems controlling catecholamine and glucocorticoid secretion. Stress-induced stimulation of CRF-containing neurons appears to be mediated by serotonergic, noradrenergic, and possibly other neuronal pathways. Stress can alter various neurobiological and endocrine functions, two essential components of the neuroendocrine responses being release of adrenalin from chromaffin cells of the adrenal medulla and secretion of glucocorticoids from adrenocortical cells. Activation of adrenal steroid secretion is mainly by a reflex activation of hypothalamic neurons, which stimulate ACTH secretion from the anterior pituitary. While the neuropeptide CRF plays a major role in the neuroendocrine response to stress, the neuronal signals which are responsible for the regulation of CRF neurons have not been completely elucidated. A number of other regulatory substances may also participate, alone or with CRF, in the control of ACTH secretion by pituitary corticotrophs, and there is increasing evidence that classical neurotransmitters or neuropeptides may act directly on adrenocortical cells to modulate corticosteroid secretion. We review the neuronal, neuroendocrine, and humoral pathways which participate in the regulation of stress-induced corticosteroid secretion, and present preliminary data on the effect of the tricyclic antidepressant, tianeptine in the response of the HPA axis to stress.

Animals↗

PubMed1991

Involvement of non-selective cationic channels in the generation of pacemaker depolarizations and firing behaviour in cultured frog melanotrophs.

The firing patterns of cultured frog melanotrophs were studied using the patch-clamp technique. In the cell-attached mode, unitary currents were frequently observed as well as biphasic waveforms which were attributed to action potentials 'leaking' through the patch membrane. An inwardly rectifying single-unit current was observed with pipette solutions containing either 100 mM K+ or 100 mM Na+. Under both conditions, these channels displayed an identical I/V relationship, yielding a unitary conductance of 110 pS. The channel opening time was extremely long (50-3000 ms) and single-channel currents showed typical relaxations, which triggered bursts of action currents. In the whole-cell configuration large (2-12 mV) fluctuations in the membrane voltage of current-clamped cells frequently occurred. The deflections appeared to result from single-channel currents. Depolarizing 'events' often led to the discharge of action potentials. Taken together, our data provide evidence for the existence of high-conductance cationic channels in frog pars intermedia cells. These channels may, at least in some cases, be responsible for the generation of pacemaker depolarizations, thereby regulating firing behaviour. It is concluded, that the current traversing a single channel can seriously affect the membrane potential and excitability of frog melanotrophs.

Action Potentials↗

PubMed1991

The novel antidepressant, tianeptine, reduces stress-evoked stimulation of the hypothalamo-pituitary-adrenal axis.

The possible effect of tianeptine, a novel antidepressant agent, on the neuroendocrine response to stress was investigated in adult male rats. Tube restraint stress for 30 min induced a marked increase of plasma ACTH and corticosterone. A single i.p. injection of tianeptine (10 mg/kg), 120 min before stress caused a significant decrease of ACTH and corticosterone levels. In order to investigate the kinetics of the effect of tianeptine, the drug was injected at various times (from 15 min to 12 h) before restraint stress. The inhibitory effect of tianeptine on stress-induced elevations of plasma ACTH and corticosterone occurred from 1 to 3 h after the injection. Administration of increasing doses of tianeptine revealed that only the highest doses (10 and 20 mg/kg) had a significant effect on stress-evoked stimulation of ACTH and corticosterone secretion. These results show that the antidepressant, tianeptine, reduces the activation of the hypothalamo-pituitary-adrenal (HPA) axis induced by restraint stress. Since depressed patients generally exhibit an elevated cortisol level, the present data suggest that part of the therapeutic properties of tianeptine could be accounted for by the effect of this antidepressant to modulate the activity of the HPA axis.

Adrenocorticotropic Hormone↗

PubMed1991

Distribution of somatostatin receptors in the cat and monkey visual cortex demonstrated by in vitro receptor autoradiography.

Somatostatin (SRIF, S14) receptors in the cat and monkey visual cortex were visualized by means of in vitro autoradiography with an iodinated agonist of SRIF, [125I-Tyr0,DTrp8]S14. The kinetics, performed on tissue sections, revealed an apparently single, saturable site (KD = 3.92 +/- 0.31 10(-10) M for the cat, and 3.82 +/- 0.28 10(-10) M for the monkey visual cortex) with pharmacological specificity for S14 and [DTrp]-substituted S14. Autoradiography, performed on frontal sections of the cat and monkey visual cortex, revealed a heterogeneous regional and laminar distribution of SRIF receptors. In cat areas 17, 18, and 19, SRIF receptors occur mainly in the supragranular layers, although small interareal and intra-areal differences are observed. The infragranular layers (V-VI) in area 19 contain a significantly higher proportion of SRIF receptors compared to both areas 17 and 18. In the antero- (AMLS) and posteromedial lateral suprasylvian area (PMLS), layers V and VI contain the highest proportion of SRIF receptors. This latter pattern is also observed in the area prostriata medially adjoining area 17 in the splenial sulcus. In the monkey visual cortex, areas 17 and 18 exhibit similar distribution patterns, SRIF receptors being primarily concentrated in layers V and VI. Neither in the cat nor the monkey visual cortex could we observe significant differences in SRIF receptor distribution between different retinotopic subdivisions within one area.

Animals↗

PubMed1991

Primary structures of the bombesin-like neuropeptides in frog brain show that bombesin is not the amphibian gastrin-releasing peptide.

Peptides displaying gastrin-releasing peptide/bombesin-like immunoreactivity were isolated in pure form from an extract of the brain of the European green frog, Rana ridibunda. The primary structure of the more abundant peptide was established as: Gly-Ser-His-Trp-Ala-Val-Gly-His-Leu-Met. NH2. This sequence shows one substitution (Ser for Asn) compared with mammalian gastrin-releasing peptide (18-27) (neuromedin C). The extract also contained gastrin-releasing peptide but bombesin was absent. The data indicate that bombesin is not the amphibian counterpart of gastrin-releasing peptide.

Amino Acid Sequence↗

PubMed1991

Identification of a peptide arising from the specific post-translation processing of secretogranin II.

The biological role of secrotogranin II is unknown but it has been suggested that the protein may function as a precursor of one or more biologically active neuroendocrine peptides. We have isolated a 33 amino acid-residue peptide from the brain of the frog Rana ridibunda that shows strong (82%) homology with human presecretogranin II-(182-204)-peptide. This region of secretogranin II has also been very strongly conserved in the rat and bovine proteins. Analysis of the nucleotide sequence of the mammalian secretogranin II cDNAs indicates that the peptide sequence is flanked by two Lys-Arg dibasic residue processing sites. It is proposed, therefore, that this fragment represents a specific product of the post-translational processing of secretogranin II and, by analogy with peptides derived from chromogranin A, may be important in the regulation of neurosecretion.

Amino Acid Sequence↗

PubMed1991

Characterization of melanotropin-release-inhibiting factor (melanostatin) from frog brain: homology with human neuropeptide Y.

A polypeptide was purified from frog brain extracts on the basis of its ability to inhibit alpha-melanotropin release from perifused frog neurointermediate lobes. Based on Edman degradation, amino acid analysis, and peptide mapping, the primary structure of this frog melanotropin-release-inhibiting factor (melanostatin) was determined to be H-Tyr-Pro-Ser-Lys-Pro-Asp-Asn-Pro-Gly-Glu-Asp-Ala-Pro-Ala-Glu-Asp-Met- Ala-Lys-Tyr-Tyr-Ser-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu-Ile-Thr-Arg-Gln-Arg- Tyr-NH2 . Frog melanostatin belongs to the pancreatic polypeptide/neuropeptide Y/peptide YY family, and the structure of this peptide differs from that of human neuropeptide Y by only one amino acid substitution in position 19. A synthetic replicate of frog melanostatin is coeluted with the native peptide on HPLC and is highly potent in inhibiting alpha-melanotropin secretion in vitro (IC50 = 60 nM).

Amino Acid Sequence↗

PubMed1991

Ontogeny of somatostatin receptors in the rat somatosensory cortex.

The distribution and density of SRIF receptors (SRIF-R) were studied during development in the rat somatosensory cortex by in vitro autoradiography with monoiodinated [Tyr0-DTrp8]S14. In 16-day-old fetuses (E16), intense labeling was evident in the intermediate zone of the cortex while low concentrations of SRIF-R were detected in the marginal and ventricular zones. The highest density of SRIF-R was measured in the intermediate zone at E18. At this stage, labeling was also intense in the internal part of the developing cortical plate; in contrast, the concentration of binding sites associated with the marginal and ventricular zones remained relatively low. Profound modifications in the distribution of SRIF-R appeared at birth. In particular, a transient reduction of receptor density occurred in the cortical plate. During the first postnatal week, the density of receptors measured in the intermediate zone decreased gradually; conversely, high levels of SRIF-R were observed in the developing cortical layers (II to VI). At postpartum day 13 (P13), a stage which just precedes completion of cell migration in the parietal cortex, the most intensely labeled regions were layers V-VI and future layers II-III. From P13 to adulthood, the concentrations of SRIF-R decreased in all cortical layers (I to VI) and the pattern of distribution of receptors at P21 was similar to that observed in the adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1991

Localization of neuropeptide Y-immunoreactive cells and fibres in the brain of the Japanese quail.

In the present study, we have demonstrated, by means of the biotin-avidin method, the widespread distribution of neuropeptide Y (NPY)-immunoreactive structures throughout the whole brain of the Japanese quail (Coturnix coturnix japonica). The prosencephalic region contained the highest concentration of both NPY-containing fibres and perikarya. Immunoreactive fibres were observed throughout, particularly within the paraolfactory lobe, the lateral septum, the nucleus taeniae, the preoptic area, the periventricular hypothalamic regions, the tuberal complex, and the ventrolateral thalamus. NPY-immunoreactive cells were represented by: a) small scattered perikarya in the telencephalic portion (i.e. archistriatal, neostriatal and hyperstriatal regions, hippocampus, piriform cortex); b) medium-sized cell bodies located around the nucleus rotundus, ventrolateral, and lateral anterior thalamic nuclei; c) small clustered cells within the periventricular and medial preoptic nuclei. The brainstem showed a less diffuse innervation, although a dense network of immunopositive fibres was observed within the optic tectum, the periaqueductal region, and the Edinger-Westphal, linearis caudalis and raphes nuclei. Two populations of large NPY-containing perikarya were detected: one located in the isthmic region, the other at the boundaries of the pons with the medulla. The wide distribution of NPY-immunoreactive structures within regions that have been demonstrated to play a role in the control of vegetative, endocrine and sensory activities suggests that, in birds, this neuropeptide is involved in the regulation of several aspects of cerebral functions.

Animals↗

PubMed1991

Distribution and characterization of immunoreactive growth hormone (GH) in the pituitary of the frog Rana ridibunda using an antiserum against purified bullfrog GH.

The presence of growth hormone (GH) in the pituitary of the frog Rana ridibunda was investigated using an antiserum raised against purified bullfrog GH. The immunofluorescence technique revealed that GH-containing cells are exclusively located in the dorsal area of the distal lobe of the pituitary. The relative abundance of these GH-positive cells, which correspond to acidophilic type 2 cells, was 18 +/- 1% of the total population of endocrine cells of the pars distalis. Frontal sections of the distal lobe indicated that GH-producing cells are distributed in an arc of a circle occupying all of the dorsal part of the lobe. At the electron microscopic level, GH-immunoreactive material was sequestered in large polymorphic granules (200-700 nm). GH was quantified in R. ridibunda pituitary extracts using a radioimmunoassay for bullfrog GH. The displacement curves obtained with serial dilutions of pars distalis extracts were not strictly parallel to the standard curve made with purified bullfrog GH. In contrast, Western blot analysis revealed that GH from R. ridibunda had a molecular weight (22 kDa) similar to that of bullfrog GH. In the pars distalis, the apparent amount of GH was 0.61 +/- 0.14 microgram per lobe, corresponding to 0.92 +/- 0.17% of total proteins in the extracts. In contrast, frog neurointermediate lobe or hypothalamus did not contain significant concentrations of immunoreactive GH (less than 0.006% of total proteins in the extracts). Taken together, these results validate the use of an antiserum to bullfrog GH to investigate the regulation of GH secretion in R. ridibunda.

Animals↗

PubMed1991

Anatomical interactions of proopiomelanocortin (POMC)-related peptides, neuropeptide Y (NPY) and dopamine beta-hydroxylase (D beta H) fibers and thyrotropin-releasing hormone (TRH) neurons in the paraventricular nucleus of rat hypothalamus.

In order to determine the nature of afferent fibres contacting thyrotropin-releasing hormone (TRH)-synthesizing neuronal cell bodies in the rat hypothalamic paraventricular nucleus, we used dual immunostaining procedures which employed antibodies to ACTH (to label proopiomelanocortin (POMC) neurons), neuropeptide Y (NPY) and dopamine-beta-hydroxylase (D beta H) and peroxidase-labeled goat anti-rabbit IgG as a first sequence and antibodies to a cryptic fragment (Phe178-Glu199) of pro-TRH (to label TRH neurons) and alkaline phosphatase-labeled goat anti-rabbit IgG as the second sequence. A rich innervation of the paraventricular nucleus by immunoreactive POMC, NPY and D beta H fibres was observed. Numerous NPY and POMC fibres were in intimate anatomic proximity and often appeared to surround in remarkable density TRH-containing cell bodies. Less frequent appositions between D beta H fibres and TRH cell bodies were detected. These results strongly suggest that TRH neurons might be regulated by POMC, NPY as well as adrenergic and/or noradrenergic systems. These interactions might be the neuroanatomical basis for the already observed effects of opiate peptides, NPY and catecholamines on TSH secretion.

Afferent Pathways↗

PubMed1991

Quantitative evaluation of octadecaneuropeptide-like immunoreactivity in hippocampus, cortex and cerebellum of long-term isolated male Wistar rats.

Quantitative evaluation of octadecaneuropeptide-like immunoreactivity (ODN-Li) was carried out in hippocampus, cortex and cerebellum of group-reared or three month isolated male Wistar rats, whether muricidal or not. ODN-Li was lower in cortex and cerebellum of isolated animals, (mainly in muricidal) than of group-reared ones. A similar trend was apparent in the hippocampus. No significant differences were observed between muricidal and non-muricidal animals. The results are discussed in terms of the involvement of the endogenous ligands of the GABA-benzodiazepine receptor complex in the integrations related to mood and behaviour.

Animals↗

PubMed1991

Benzamide derivatives provide evidence for the involvement of a 5-HT4 receptor type in the mechanism of action of serotonin in frog adrenocortical cells.

We have previously shown that serotonin (5-HT) is a potent stimulator of corticosterone and aldosterone secretion by frog adrenocortical cells and we have demonstrated that the action of 5-HT is not mediated by the classical 5-HT receptor subtypes i.e. 5-HT1, 5-HT2 and 5-HT3. Recently, a non-classical 5-HT receptor (termed 5-HT4) has been characterized using 4-amino-5-chloro-2-methoxy-benzamide derivatives as serotonergic agonists. In the present report, we have investigated the possible involvement of the 5-HT4 receptor subtype in the mechanism of action of 5-HT on steroid secretion. Increasing concentrations of benzamide derivatives (zacopride, cisapride and BRL 24924) gave rise to a dose-related stimulation of corticosteroid production, zacopride being the most potent compound of this series to enhance steroidogenesis. Prolonged administration (230 min) of zacopride induced a rapid increase in corticosterone and aldosterone output followed by a gradual decline of corticosteroid secretion. During prolonged exposure of adrenal tissue to zacopride (10(-5) M), the corticotropic activity of 5-HT (10(-6) M) was totally abolished. The stimulatory effects of 5-HT and zacopride were abolished by the non-selective 5-HT3 antagonist ICS 205 930. In contrast methysergide, a 5-HT1 receptor antagonist, and MDL 72222, a selective 5-HT3 antagonist did not block zacopride-induced corticosteroid secretion. Both 5-HT and zacopride induced a dose-related increase in cAMP production by frog adrenal slices. Taken together, these results indicate that the stimulatory effect of 5-HT on frog adrenocortical tissue is mediated by activation of a 5-HT4 receptor subtype positively coupled to adenylate cyclase.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1991

Dopamine-induced inhibition of action potentials in cultured frog pituitary melanotrophs is mediated through activation of potassium channels and inhibition of calcium and sodium channels.

A patch-clamp study was conducted in order to investigate the effects of dopamine on the ionic currents in cultured frog melanotrophs. Brief applications of dopamine (1 microM) hyperpolarized the cell and inhibited the spontaneous action potentials. The hyperpolarization was accompanied by an increase in membrane conductance. Under voltage clamp, dopamine evoked a net outward current. The dopamine-induced outward current was negligible at the equilibrium potential for potassium ions. It was also observed that dopamine increased the intensity of a voltage-dependent outward potassium current monitored by constant depolarizing pulses. In addition, voltage-dependent L- and N-like calcium currents and sodium current were reduced. In the cell-attached configuration, two distinct channel types were activated and one channel type was blocked by dopamine exposure to the extrapatch membrane, which indicates the involvement of an intracellular factor in the signal transduction pathway. A higher conductance channel (100 pS) was characterized by a very low basal activity which rapidly increased upon dopamine application. A lower conductance channel (30 pS) displayed a basal activity with frequent opening events, and a delayed (30-40 s) increase of activity in response to dopamine. Both currents reversed at a deduced potential corresponding to the equilibrium potential for potassium ions. The channel type inhibited by dopamine had a low conductance of 15 pS. The inhibition of the electrical activity induced by dopamine was totally blocked by the D2 receptor antagonist S(-)-sulpiride (1 microM) but was not affected by the D1 receptor antagonist SKF-83566 (1 microM). It is concluded that dopamine activates potassium channels and inhibits calcium and sodium channels in frog melanotrophs. The results also indicate that stimulus-response coupling is mediated by intracellular messenger system(s).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗