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H Vaudry

Publications and source records attributed to H Vaudry.

621 records · Page 35Linked to original sources

Pharmacological profile of serotonergic receptors in the adrenal gland.

The secretory activity of the adrenal gland is mainly regulated by peptidergic hormones (ACTH, angiotensin II) and ions. However, there is now increasing evidence that local factors, including neuropeptides and neurotransmitters, can also participate in the control of adrenocortical cells. In particular, serotonin (5-HT), produced by adrenochromaffin cells in frog and rat as well as by mast cells in the adrenal gland of rat and human, stimulates corticosteroid secretion. In both frog and human adrenal gland, the benzamide derivative (R,S)-zacopride induces a robust increase in corticosteroid release suggesting that the effect of 5-HT on steroidogenesis is mediated through activation of 5-HT4 receptors. In contrast, in rat, the stimulatory effect of 5-HT on aldosterone secretion is clearly not mediated by 5-HT4 receptors. In all three species, incubation of adrenocortical fragments with 5-HT induces a significant increase in cAMP formation. Our data suggest that 5-HT, released within the adrenal cortex, may act as a paracrine factor to stimulate steroid secretion. Although the corticotropic effect of 5-HT has been conserved from amphibians to primates, the type of receptors involved in the action of 5-HT markedly differs across species.

Adrenal Cortex Hormones↗

Identification of a novel secretogranin II-derived peptide in the adult and fetal human adrenal gland.

Molecular cloning of secretogranin II (SgII) in different species has revealed the existence of a highly conserved 66-amino acid peptide (EM66) flanked by preserved pairs of basic residues. In the present study we have localized and characterized EM66 in the human adrenal gland. A fusion protein containing the human EM66 peptide was produced in E. coli and used to raise polyclonal antibodies in rabbits. Immunohistochemical staining of human adrenal slices revealed intense labeling of adrenochromaffin cells in the adult and fetal gland. HPLC analysis of adrenal extracts showed the presence of an immunoreactive peak exhibiting the same retention time as recombinant EM66 in both adult and fetus. These data demonstrate that post-translational processing of SgII actually generates a novel peptide in the human adrenal gland. The conservation of the sequence of EM66 in vertebrates and the occurrence of the mature peptide during early ontogenesis of the human adrenal gland strongly suggest that EM66 could exert physiological activities.

Adrenal Glands↗

Effect of prolonged administration of the serotonin4 (5-HT4) receptor agonist cisapride on aldosterone secretion in healthy volunteers.

In man, serotonin (5-HT) has been shown to stimulate aldosterone secretion through activation of 5-HT4 receptors, In particular, we have observed that oral administration of a single dose of the 5-HT4 receptor agonist cisapride (10 mg) induces a 5-fold increase in plasma aldosterone levels in healthy volunteers. Surprisingly, the usual disorders associated with hyperaldosteronism, i.e. hypertension and hypokalemia, have never been reported during chronic treatment with cisapride. In the present study, we have investigated the effect of prolonged oral administration of cisapride (10 mg, 3 times/day during 7 days) on aldosterone secretion in 12 healthy volunteers, in a simple blind fashion versus placebo. On day 1 of the treatment, cisapride induced a significant increase in plasma aldosterone levels (PAL) which returned to the values observed after placebo treatment within 10 hrs. On days 2 and 3, PAL were similar in cisapride- and placebo-treated subjects. Urinary aldosterone, kalemia and reninemia were not influenced by cisapride during the 7 days of the treatment. The present study shows that cisapride only exerts a transient stimulatory effect on aldosterone secretion in healthy volunteers. These data explain why long-term administration of 5-HT4 agonists does not affect blood pressure in man. They also indicate that prolonged stimulation of adrenal 5-HT4 receptors in vivo yields to a rapid desensitization phenomenon, as previously observed in vitro.

Aldosterone↗

Synthesis, receptor binding affinities and alpha-MSH releasing activities of TRH analogues.

New syntheses of three thyrotropin releasing hormone (TRH) analogues ([Dopa2]THR, [Nic1]TRH, and [Tyr(30NO2)2]TRH) have been reported (Dopa stands for L-3,4-dihydroxyphenylalanine, Nic--for nicotinic acid and Tyr(3-NO2)--for L-3-nitrotyrosine). These three TRH analogues and five already known ones ([Aad1Tca3]TRH, [D-His2]TRH, [D-Pro3]TRH, [Pro-NH-NH2(3)]TRH and [Tyr2]TRH), were studied in vitro for their binding activity to rat pituitary TRH receptors and a-MSH releasing activity in the neuro-intermediate lobe of frogs. Competition of analogues for 3H-TRH binding to rat anterior pituitary membrane fraction was used. One of ten tested analogues ([Aad1, Tca]3 TRH) was as potent as TRH in competing for high-affinity binding sites (Kd = 8.5 nM). The binding activity of diastereoisomers ([D-His2]TRH and [D-Pro3]TRH) was reduced as well as that of analogue [Pro-NH-NH2(3)]TRH. The rest of the analogues were inactive. The binding activities were in good accordance with alpha-MSH releasing activities.

Animals↗

[Plasma assay of somatocrinin during growth hormone stimulation tests. Results in pediatrics].

Somatocrinin (GHRH) levels were measured by RIA in the plasma of 41 children with constitutionally short stature. Basal plasma GHRH level was 51 +/- 10 pg/ml. L-Dopa induced a two fold increase in circulating GHRH levels 30 to 45 minutes before the elevation of GH. A positive correlation (p less than 0.005) was found between the peak of GH and GHRH levels during the dopaminergic stimulus. Conversely, the secretion of GH induced by amino-acids or clonidine was not preceded by an elevation of GHRH. These results suggest that the various stimulations of GH secretion used for investigations of short stature do not act in the same way at the hypothalamo-pituitary level.

Amino Acids↗