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H Vaudry

Publications and source records attributed to H Vaudry.

At least 397 records · Page 22Linked to original sources
PubMed1990

Atrial natriuretic factor increases cyclic GMP and cyclic AMP levels in a directly photosensitive pineal organ.

Atrial natriuretic factor (ANF) stimulates accumulation of cyclic GMP in a photosensitive organ, as evidenced for the first time in cultured trout pineals. Stimulation was rapid (within a few min), dose-dependent, and stronger in organs cultured in darkness than in those cultured under light. After 30 min in the dark, (i) cyclic AMP levels were slightly increased at 10(-7) mole/l of ANF, (ii) cyclic GMP and cyclic AMP increased dramatically after inhibition of the phosphodiesterases by isobutylmethylxanthine (IBMX), (iii) ANF and IBMX effects were more than additive on cyclic GMP, (iv) pertussis toxin decreased the cyclic GMP response to ANF. These responses were affected by light. The possibility that cyclic GMP might be a second messenger of both light and chemical (ANF) inputs, in pineal photoreceptor cells, is hypothetized.

1-Methyl-3-isobutylxanthine↗
PubMed1990

GABA neurons in the rat suprachiasmatic nucleus: involvement in chemospecific synaptic circuitry and evidence for GAD-peptide colocalization.

Dual labelling methods were employed for the electron microscopic detection of glutamate decarboxylase (GAD) immunoreactivity, together with vasoactive intestinal peptide (VIP) or neuropeptide Y (NPY) immunoreactivity in the suprachiasmatic nucleus (SCN) of colchicine pretreated and untreated rats. These methods involved the combined use of diaminobenzidine and benzidine dihydrochloride as distinct chromogens to visualize peroxidase-anti-peroxidase (PAP) immunostaining, and a combination of the PAP procedure with a radioimmunocytochemical method employing 125I-labelled secondary antisera. We were thereby able to demonstrate that gamma-aminobutyric acid (GABA) terminals provide an important afferent synaptic input to VIP neurons. Some of these VIP-immunoreactive neurons also exhibited GAD immunoreactivity. Examples of direct appositions between GABA and NPY terminals, and of a convergence of the two types of terminals on to the same postsynaptic targets, were frequently encountered. NPY/GAD colocalization within a few axonal varicosities was also demonstrated. These data provide additional information concerning chemospecific neuronal interactions that could be of functional importance in the regulation of circadian rhythmicity at the level of the SCN.

Animals↗
PubMed1990

CRF, urotensin I, and sauvagine stimulate the release of POMC-derived peptides from goldfish neurointermediate lobe cells.

In teleost fishes, the melanotropes of the neurointermediate lobe of the pituitary gland release numerous peptides--adrenocorticotropin (ACTH), melanotropin (MSH), lipotropin (LPH), corticotropin-like intermediate lobe peptide (CLIP), and endorphin--which are derived from the precursor molecule proopiomelanocortin. Superfused, isolated, dispersed goldfish neurointermediate lobe cell columns were used to investigate the release of immunoreactive (ir) alpha-MSH and ir ACTH from goldfish melanotropes. Stimulation of neurointermediate lobe cell columns with pulses of the structurally homologous peptides, Catostomus urotensin I (UI), ovine corticotropin-releasing factor (oCRF), or sauvagine, produced a significant increase in the concomitant release of ir alpha-MSH and ir ACTH. UI was two to three times as potent as ovine CRF or sauvagine. These studies suggest that CRF- and UI-like peptides stimulate the secretory activity of teleost melanotropes.

Adrenocorticotropic Hormone↗
PubMed1990

Adrenal activity in the female lizard Lacerta vivipara jacquin associated with breeding activities.

Variations of adrenal activity were studied in captive viviparous females Lacerta vivipara, in relation to breeding activities. The study was restricted to the period of active life which includes both the phase of annual reproduction and a phase of sexual inactivity. Significant seasonal changes in plasma corticosterone levels were measured with a peak during the second half of gestation followed by an abrupt fall at parturition. No significant variations in plasma aldosterone levels were observed. A limited extraovarian production of progesterone was detected which might be of adrenal origin. The half-life of injected tritiated corticosterone was not longer in pregnant than in nonreproductive females, suggesting that the peak of circulating corticosterone in pregnant females corresponds to an increase in the production rate of the hormone. The functional importance of the pituitary-adrenal axis was demonstrated in vivo: plasma corticosteroid levels dropped to the detection limit after adenohypophysectomy. Seasonal variations of adrenal sensitivity to synthetic ACTH 1-39 were examined in vitro, using a perifusion system. No significant variations were observed throughout the period of active life. These results suggest that the peak of plasma corticosterone during gestation can be ascribed to activation of the pituitary-adrenal axis. Experimental modifications of circulating corticosterone level during late gestation altered the timing of parturition, thus indicating that the fall of corticosterone just before term may be involved in the process of parturition in the female L. vivipara.

Adrenal Glands↗
PubMed1990

Adrenal activity in the female lizard Lacerta vivipara Jacquin during artificial hibernation.

The variations of interrenal activity were investigated in captive female Lacerta vivipara submitted to artificial hibernation (4 months at 6 degrees) and compared to data obtained in nonhibernating females. Plasma corticosterone levels reached 25 ng/ml during the prehibernal period. During the first day following the transfer to cold conditions, an initial significant peak of plasma corticosterone was observed (up to 63 ng/ml). A second, more gradual, but also significant increase was observed thereafter and levels remained maximum during the two first months of artificial hibernation (75 ng/ml). The circulating levels of corticosterone then decreased gradually. At the time of transfer to warm conditions, a third significant peak of corticosterone was observed (up to 82 ng/ml). The minimal values (15 ng/ml) previously described during vitellogenesis were reached within 1 week. High corticosterone levels appeared to be actually related to the "hibernation state" since they were also observed in hibernating males and not in nonhibernating females. In order to explain the pattern of plasma corticosterone, variations of adrenal sensitivity to synthetic ACTH 1-39 were examined in vitro, using a perifusion system technique. Surprisingly, ACTH-induced stimulation of corticosterone and aldosterone release was significantly reduced during hibernation, whatever the temperature of the perifusion bath (30 or 6 degrees). Nevertheless, a fourfold increase in the half-life of injected tritiated corticosterone was observed during hibernation which likely contributes to maintain high levels of corticosterone despite a low production rate of the hormone.

Adrenal Glands↗
PubMed1990

Neuropeptide Y inhibits thyrotropin-releasing hormone-induced stimulation of melanotropin release from the intermediate lobe of the frog pituitary.

Previous studies have shown that the release of melanotropin from frog neurointermediate lobes is under the control of two neuropeptides: thyrotropin-releasing hormone (TRH) stimulates, while neuropeptide Y (NPY) inhibits alpha-melanocyte-stimulating hormone (alpha-MSH) secretion from intact neurointermediate lobes in vitro. The aim of the present study was to investigate possible interactions between the two regulatory peptides at the pituitary level. Whole neurointermediate lobes or acutely dispersed pars intermedia cells from Rana ridibunda were perifused in vitro for 2 to 7.5 hr and the concentrations of alpha-MSH released into the effluent perifusate were monitored by radioimmunoassay. Administration of TRH (10(-7) M) or NPY (10(-7) M) to dispersed cells induced, respectively, marked stimulation or inhibition of alpha-MSH release. The effects of the two neuropeptides were similar to those observed using intact neurointermediate lobes, suggesting that TRH and NPY act directly on melanotropic cells. Perifused whole neurointermediate lobes were exposed to NPY (10(-8) to 3 x 10(-7) M) for 120 min and a single dose of TRH (10(-8) M) was administered during the prolonged infusion of NPY. Using this procedure, we observed a dose-dependent inhibition of TRH-evoked alpha-MSH release. These data support the concept that TRH and NPY act through a common intracellular pathway to regulate alpha-MSH release.

Animals↗
PubMed1990

Structure-activity relationships of monomeric and dimeric synthetic ACTH fragments in perifused frog adrenal slices.

The effect of synthetic monomeric and dimeric ACTH fragments on spontaneous and ACTH(1-39)-evoked steroidogenesis in frog interrenal tissue was studied in vitro. Infusion of ACTH fragment 11-24 (10(-6) M) or its dimeric conjugates, attached either by their N-terminal, Glu(11-24)2, or their C-terminal amino acid, (11-24)2Lys, had no effect on the spontaneous release of corticosteroids. The monomer ACTH(11-24) and the dimer Glu(11-24)2 were also totally devoid of effect on the steroidogenic response to ACTH(1-39) (10(-9)M). In contrast, the (11-24)2Lys conjugate (10(-6)M) significantly decreased ACTH-induced stimulation of corticosterone and aldosterone (-63 and -62%, respectively). The dimeric conjugate of the fragment ACTH(7-24), linked through the C-terminal ends, (7-24)2Lys (10(-6)M), was also completely devoid of effect on basal steroidogenesis but caused a marked decrease of ACTH-evoked corticosterone and aldosterone release (-72 and -80%, respectively). Conversely, infusion of the dimer (1-24)2Lys gave rise to a dose-related stimulation of corticosterone and aldosterone release. The time-course of the steroidogenic response to the dimer was similar to that of ACTH(1-24). The 1-24 conjugate was 70 times less potent than the monomers ACTH(1-24) and ACTH(1-39). These results suggest that amphibian adrenocortical cells contain only one class of ACTH receptor which recognizes the 11-24 domain of ACTH with an affinity which depends on the presence of a strong potentiator segment, located at the N-terminus end of ACTH(1-39). Since the ACTH-dimers are thought to induce cross-linking of the receptors, our results suggest that aggregation of ACTH receptors causes a down-regulation of the receptors.

Adrenal Glands↗
PubMed1990

Immunocytochemical localization of the endogenous benzodiazepine ligand octadecaneuropeptide (ODN) in the rat brain.

In order to study the morphological localization of the endogenous benzodiazepine ligand octadecaneuropeptide (ODN) in rat brain, we have developed antibodies against this peptide. Using a radioimmunoassay for ODN, we have observed that synthetic ODN and serial dilutions of several brain areas gave parallel displacement curves. By light microscope immunocytochemistry, ODN-immunoreactive material was only detected in glial and ependymal cells. Immunolabelled cells were found in high concentrations in the olfactory bulb, hypothalamus, hippocampus, periaqueductal gray, cerebral cortex and the circumventricular organs. In the cerebellar cortex, immunostaining was associated with Bergmann cells. The studies performed at the electron microscopic level confirmed the association of immunoreactive material with glial and ependymal cells. The present results suggest that ODN might play a role in the function of glial cells which have been shown to contain benzodiazepine receptors of the "peripheral type".

Animals↗
PubMed1990

Effects of ions and ionic channel activators or blockers on release of alpha-MSH from perifused rat hypothalamic slices.

The involvement of sodium and chloride ions in the process of alpha-melanocyte-stimulating hormone (a-MSH) release from hypothalamic neurons was investigated using perifused rat hypothalamic slices. Three different stimuli were found to increase a-MSH release from hypothalamic slices: high K+ concentration (50 mM), veratridine (50 microM), and the Na+/K(+)-ATPase inhibitor ouabain (1 mM). Spontaneous or K(+)-evoked a-MSH release was insensitive to the specific Na+ channel blocker tetrodotoxin (TTX; 1.5 microM) and to the blocker of K+ channels tetraethylammonium (TEA; 30 mM) or 4-aminopyridine (4-AP; 4 mM). In contrast, blockage of ouabain-sensitive Na+/K(+)-ATPase increased the resting level of a-MSH and caused a dramatic potentiation of K(+)-evoked a-MSH release. The Na+ channel activator veratridine (50 microM) triggered a-MSH release. This stimulatory effect was blocked by TTX and prolonged by TEA application, indicating the occurrence of voltage-sensitive Na+ and K+ channels on a-MSH neurons. Replacement of Na+ by impermeant choline ions from 95 to 60 mM did not alter K(+)-evoked a-MSH release. Conversely, dramatic reduction of the external Na+ concentration to 16 mM caused a robust increase of a-MSH secretion from hypothalamic neurons, likely through activation of the Na+/Ca2+ exchange system. These data indicate that the depolarizing effect of K+ results from direct activation of voltage-operated Ca2+ channels. The lack of effect of TEA on basal a-MSH release prompted us to investigate the possible involvement of chloride ions in the regulation of the spontaneous activity of a-MSH neurons. Substitution of Cl- for impermeant acetate ions did not affect basal or K(+)-evoked a-MSH release.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1990

GABA and neuropeptide Y co-exist in axons innervating the neurointermediate lobe of the pituitary of Xenopus laevis--an immunoelectron microscopic study.

The neural innervation of the neurointermediate lobe of the pituitary of the amphibian Xenopus laevis has been studied at the light and electron microscopic level. In the pars intermedia melanotropes and stellate cells are abutted by varicosities originating from GABA- and neuropeptide Y-producing neurons. The varicosities contain two types of vesicle: electron-lucent vesicles (mean diameter 50 nm) which are immunopositive for GABA and larger (80 nm) electron-dense vesicles which are immunopositive for neuropeptide Y. Double immunogold labeling established that GABA and neuropeptide Y co-exist within the varicosities. In the pars nervosa similar varicosities, though low in number, occur. They are associated with neurosecretory nerve terminals, pituicytes and blood vessels. The possible significance of GABA and neuropeptide Y for the neural regulation of melanophore stimulating hormone-release from the pars intermedia is discussed.

Animals↗
PubMed1990

Processing of thyrotropin-releasing hormone prohormone (pro-TRH) generates a biologically active peptide, prepro-TRH-(160-169), which regulates TRH-induced thyrotropin secretion.

Rat thyrotropin-releasing hormone (TRH) prohormone contains five copies of the TRH progenitor sequence Gln-His-Pro-Gly linked together by connecting sequences whose biological activity is unknown. Both the predicted connecting peptide prepro-TRH-(160-169) (Ps4) and TRH are predominant storage forms of TRH precursor-related peptides in the hypothalamus. To determine whether Ps4 is co-released with TRH, rat median eminence slices were perifused in vitro. Infusion of depolarizing concentrations of KCl induced stimulation of release of Ps4- and TRH-like immunoreactivity. The possible effect of Ps4 on thyrotropin release was investigated in vitro using quartered anterior pituitaries. Infusion of Ps4 alone had no effect on thyrotropin secretion but potentiated TRH-induced thyrotropin release in a dose-dependent manner. In addition, the occurrence of specific binding sites for 125I-labeled Tyr-Ps4 in the distal lobe of the pituitary was demonstrated by binding analysis and autoradiographic localization. These findings indicate that these two peptides that arise from a single multifunctional precursor, the TRH prohormone, act in a coordinate manner on the same target cells to promote hormonal secretion. These data suggest that differential processing of the TRH prohormone may have the potential to modulate the biological activity of TRH.

Amino Acid Sequence↗
PubMed1990

Pharmacological characterization of somatostatin receptors in the rat cerebellum during development.

Somatostatin (SRIF) receptors (SRIF-Rs) are transiently expressed in a germinative lamina of the rat cerebellum, the external granule cell layer. The appearance of SRIF-Rs coincides with the expression of SRIF-like immunoreactivity in the cerebellum. However, the cellular location of SRIF-Rs does not overlap with the distribution of SRIF-like immunoreactivity, with the latter being restricted to ascending fibers arising from the brainstem, to perikarya within the white matter, and to some Purkinje cells. The characterization of SRIF-Rs in the immature (13-day-old) rat cerebellum was conducted by means of binding experiments in membrane-enriched preparations and autoradiography, using two radioligands, [125I-Tyr0,D-Trp8]SRIF-14 [( 125I-Tyr0,D-Trp8]S14) and 125I-SMS 204-090. The pharmacological profile of cerebellar SRIF-Rs was compared with that of adult cortical SRIF-Rs. Saturation studies performed in 13-day-old rat cerebellum showed that the KD values for [125I-Tyr0,D-Trp8]S14 and 125I-SMS 204-090 binding were 0.35 +/- 0.04 and 0.39 +/- 0.01 nM, respectively. The corresponding Bmax values were 52.7 +/- 4.8 and 49.9 +/- 5.3 fmol/mg of protein, a result indicating that radioligands with high specific radioactivity (2,000 Ci/mmol) bind to a single class of high-affinity sites (SS1). Competition studies showed that different D-Trp-substituted analogs displaced [125I-Tyr0,D-Trp8]S14 binding with Hill coefficients less than 1, a finding indicating the existence of different subtypes of binding sites. When [Tyr0,D-Trp8]S14 was used as a competitor, two sites were resolved by Scatchard analysis in both 13-day-old cerebellum and adult cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Neuropeptide Y: localization in the central nervous system and neuroendocrine functions.

Neuropeptide Y (NPY) is a 36-amino acid peptide first isolated and characterized from porcine brain extracts. A number of immunocytochemical investigations have been conducted to determine the localization of NPY-containing neurons in various animal species including both vertebrates and invertebrates. These studies have established the widespread distribution of NPY in the brain and in sympathetic neurons. In the rat brain, a high density of immunoreactive cell bodies and fibers is observed in the cortex, caudate putamen and hippocampus. In the diencephalon, NPY-containing perikarya are mainly located in the arcuate nucleus of the hypothalamus; numerous fibers innervate the paraventricular and suprachiasmatic nuclei of the hypothalamus, as well as the paraventricular nucleus of the thalamus and the periaqueductal gray. At the electron microscope level, using the pre- and post-embedding immunoperoxidase techniques, NPY-like immunoreactivity has been observed in neuronal cell body dendrites and axonal processes. In nerve terminals of the hypothalamus, the product of the immunoreaction is associated with large dense core vesicles. In lower vertebrates, including amphibians and fish, neurons originating from the diencephalic (or telencephalic) region innervate the intermediate lobe of the pituitary where a dense network of immunoreactive fibers has been detected. At the ultrastructural level, positive endings have been observed in direct contact with pituitary melanotrophs of frog and dogfish. These anatomical data suggest that NPY can act both as a neurotransmitter (or neuromodulator) and as a hypophysiotropic neurohormone. In the rat a few NPY-containing fibers are found in the internal zone of the median eminence and high concentrations of NPY-like immunoreactivity are detected in the hypothalamo-hypophyseal portal blood, suggesting that NPY may affect anterior pituitary hormone secretion. Intrajugular injection of NPY causes a marked inhibition of LH release but does not significantly affect other pituitary hormones. Passive immunoneutralization of endogenous NPY by specific NPY antibodies induces stimulation of LH release in female rats, suggesting that NPY could affect LH secretion at the pituitary level. However, NPY has no effect on LH release from cultured pituitary cells or hemipituitaries. In addition, autoradiographic studies show that sites for 125I-labeled Bolton-Hunter NPY or 125I-labeled PYY (2 specific ligands of NPY receptors) are not present in the adenohypophysis, while moderate concentrations of these binding sites are found in the neural lobe of the pituitary. It thus appears that the inhibitory effect of NPY on LH secretion must be mediated at the hypothalamic level.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Dopamine inhibits corticosteroid secretion from frog adrenal gland, in vitro.

The effect of dopamine on corticosteroid secretion from frog interrenal (adrenal) tissue was investigated in vitro using a perifusion system technique. Administration of graded concentrations of dopamine (5 X 10(-8) M to 10(-3) M) to interrenal slices induced a dose-dependent inhibition of steroid secretion. The half-maximal effective dose of dopamine was 7 X 10(-6) M for corticosterone and 4 X 10(-6) M for aldosterone. Noradrenaline and adrenaline were also able to elicit a dose-related inhibition of steroid release, but these catecholamines were approximately 100 and 2000 times less potent than dopamine in our model. Administration of repeated pulses of dopamine (5 X 10(-5) M), at 150-min intervals, led to a reproducible inhibition of corticosteroid secretion without any desensitization phenomenon. Similarly, prolonged infusion of dopamine (5 X 10(-6) M) caused a sustained inhibition of steroidogenesis. The inhibitory action of dopamine was also observed using enzymatically dispersed adrenal cells, indicating that dopamine exerts a direct effect on adrenocortical cells. After the second pulse, dopamine also induced a transient stimulation of steroid secretion from acutely dispersed cells. Administration of short pulses of apomorphine (5 X 10(-5) M) induced a transient inhibition of corticosteroid secretion, and the kinetics of the response were very similar to that observed with dopamine. During prolonged administration of dopamine, the steroidogenic actions of ACTH (10(-9) M) and serotonin (5 X 10(-6) M) were not altered. In contrast, dopamine induced a marked inhibition of angiotensin II-evoked corticosteroid secretion. Taken together, these results show that the neurotransmitter dopamine exerts a direct inhibitory effect on steroid secretion from frog adrenocortical cells. Our results also indicate that dopamine and angiotensin II likely act through a common intracellular pathway. These data suggest that dopamine, released by chromaffin cells during neurogenic stress, may modulate the response of adrenocortical cells through a paracrine mode of communication.

Adrenal Cortex Hormones↗
PubMed1990

Processing of thyrotropin-releasing hormone (TRH) prohormone in the rat olfactory bulb generates novel TRH-related peptides.

Based on the deduced amino acid sequence of rat TRH prohormone (pro-TRH), proteolytic processing of this polyprotein precursor is expected to produce, beside TRH, several other novel peptides. These peptides should correspond to connecting segments flanking the repeated TRH progenitor sequence and to various C- and/or N-terminally extended forms of TRH. The profile of the endogenous products of the TRH system was studied in rat brain using multiple RIAs coupled to molecular sieve filtration and HPLC separations. In extracts from the rat hypothalamus, TRH and two pro-TRH-connecting peptides, prepro-TRH-(160-169) and prepro-TRH-(178-199) were detected in molar ratios corresponding to those expected for a nearly complete processing of the prohormone molecule. In the olfactory bulb, pro-TRH is processed differently, since peptides containing TRH at their N-termini, [pGlu172] prepro-TRH-(172-199) and [pGlu154]prepro-TRH-(154-169), were found to be major end products along with prepro-TRH-(160-169) and prepro-TRH-(178-199). The dissimilarity in tissue content suggests that differential processing of TRH precursor by various enzymatic pathways may act as a regulating mechanism for TRH and TRH-related activities. The cellular localization of C-terminally extended forms of TRH in rat olfactory bulb was examined by the indirect immunoperoxidase method, using antisera directed against prepro-TRH-(160-169) and pre-pro-TRH-(178-199). Cell bodies and nerve fibers were detected in the glomerular and external plexiform layers of the main olfactory bulb. The presence of extended forms of TRH in interneurons and middle tufted cells of the main olfactory bulb suggests that in light of the recent biological properties described for prepro-TRH-(160-169), these peptides may act as neuromodulators for olfactory epithelium inputs or neurotransmitters within more rostrally located olfactory areas in the forebrain.

Amino Acid Sequence↗
PubMed1990

Localization of the endogenous benzodiazepine ligand octadecaneuropeptide in the rat testis.

Diazepam binding inhibitor (DBI) is the precursor of a family of peptides, including an octadecaneuropeptide (ODN), which share with DBI the ability to specifically displace benzodiazepines (BZD) from their receptors. BZD receptors have been found not only in the brain, but also in a variety of peripheral tissues, including the testis. To clarify the role of ODN in the testis, we have investigated the localization of ODN in the rat testis using two different cytochemical approaches: immunocytochemistry and in situ hybridization. Immunocytochemical localization was achieved using rabbit antibodies developed against rat ODN. At the light microscopic level, immunostaining was exclusively located in interstitial cells; the seminiferous tubules were totally unlabeled. In the developing rat, immunostaining in the interstitial cells was first detected in an 18-day-old fetus. The immunolabeling increased as a function of age to reach a plateau at 40 days of age. The ultrastructural localization of ODN was achieved by immunogold staining. The gold particles were exclusively found in the cytoplasm of Leydig cells. HPLC analysis performed in adult rat testicular extracts revealed that immunoreactive material was detected in a peak eluted later than synthetic rat ODN. The cellular distribution of ODN was also studied by in situ hybridization using a 35S-labeled single stranded RNA probe complementary to DBI mRNA. Hybridization signal obtained at the light microscopic level was only detected over interstitial cells. The data obtained clearly indicate that in the rat, Leydig cells synthesize ODN and accumulate ODN-like immunoreactivity. Since Leydig cells have been shown to contain BZD receptors, it might be hypothesized that ODN and/or other DBI-related peptides can play a role in Leydig cell regulation.

Animals↗
PubMed1990

Endothelin stimulates steroid secretion by frog adrenal gland in vitro: evidence for the involvement of prostaglandins and extracellular calcium in the mechanism of actin of endothelin.

Endothelin (ET-1) is a pleiotropic regulatory peptide which exerts multiple endocrine actions on the cardiovascular system. In the present study, we have investigated the possible role of ET-1 in the regulation of adrenocortical cells using perifused frog interrenal (adrenal) slices. Graded doses of ET-1 from 10(-11)-10(-9) M stimulated both corticosterone and aldosterone production in a dose-dependent manner. Repeated 20-min pulses of ET-1 (10(-9) M), given at the frequency of one pulse per 90 min, resulted in a marked reduction of the secretory response after the second pulse. Prolonged administration (3 h) of ET-1 induced a rapid increase in corticosterone and aldosterone output, followed by a gradual decline of corticosteroid secretion. Perifusion of frog adrenal tissue with ET-1 (10(-9) M) caused a significant increase in the release of prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha, the stable metabolite of the prostacyclin PGI2. The enhancement of PG biosynthesis preceded by 10 min the peak of corticosteroids. When repeated pulses of ET-1 were administered, a significant diminution of the production of PGE2 and 6-keto-PGF1 alpha was observed after the second pulse. The cyclooxygenase inhibitor indomethacin (5 microM) totally suppressed the stimulatory effect of ET-1 on corticosterone and aldosterone secretion; in contrast, indomethacin did not affect ACTH-evoked corticosteroid secretion. Perifusion of adrenal slices with a calcium-free solution or addition of cobalt (4 mM) induced total inhibition of the stimulatory effect of ET-1. These results demonstrate that ET-1 is a potent stimulator of corticosterone and aldosterone secretion from frog adrenal gland in vitro. Our data show that repeated or prolonged administration of ET-1 induces a rapid desensitization phenomenon. The data also indicate that ET-1-evoked corticosteroid secretion is mediated by an increase in PG biosynthesis and requires the presence of extracellular calcium.

6-Ketoprostaglandin F1 alpha↗