Central Stimulation of Renin Secretion through Serotonergic, Noncardiovascular Mechanisms

Serotonin (5-HT) stimulates aldosterone secretion in man through activation of 5-HT₄ receptors coupled to adenylyl cyclase via a Gs regulatory protein. In adrenocortical cells, the levels of expression of the Gs protein and ACTH receptor are decreased when the cells are deprived of ACTH and angiotensin II (ANGII). In order to examine the possible influence of ACTH and ANGII on the responsiveness of human glomerulosa cells to 5-HT, we have investigated the effect of cisapride, a 5-HT4 receptor agonist, on plasma aldosterone in patients with suppressed plasma ACTH, i.e. patients with corticotropic insufficiency (CI), and in patients with suppressed renin-ANG II activity, i.e. patients with primary hyperaldosteronism (PH) including both aldosterone-producing adenoma and idiopathic hyperaldosteronism. After 2 h of recumbency, all patients received a single oral dose of 10 mg cisapride. In the CI group, cisapride induced a 5-fold increase in plasma aldosterone levels without any modification of plasma renin, potassium or cortisol levels. Combined administration of cisapride and ACTH caused an increase in plasma aldosterone similar to that produced by ACTH alone. In the PH group, cisapride was still able to cause a 3.6-fold increase in plasma aldosterone levels while renin remained suppressed throughout the study. Taken together, these data show that cisapride stimulates aldosterone secretion in CI and PH patients, indicating that prolonged suppression of plasma ACTH or renin-ANG II activity does not affect the sensitivity of glomerulosa cells to 5-HT. The present study also demonstrates that the stimulatory effects of 5-HT and ACTH on aldosterone secretion are not additive.

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“…8]; (iii) 5-HT increases plasma renin activity [9,10]; (iv) 5-HT directly stimulates adrenal glomerulosa cells [4,[11][12][13][14][15].…”

Section: Administration Of Serotonin (5-ht) or Its Precursors Tryptopmentioning

confidence: 99%

Effect of the Serotonin 5-HT<sub>4</sub> Receptor Agonist Cisapride on Aldosterone Secretion in Corticotropic Insufficiency and Primary Hyperaldosteronism

Lefebvre¹,

Dhib

Godin

et al. 1997

Neuroendocrinology

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“…In particular, 5-HI is involved in the circadian rhythmicity of ACTH secretion (9) and in the activation of the hypothalamo-pituitary-adrenal axis during stress (10). 5-HTcan also activate the renin-angiotensin system by stimulating renin secretion and, consequently, may indirectly enhance aldosterone production (11). At the adrenal level, 5-HT is able to stimulate corticosteroid secretion in various species including man (12)(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Serotonergic Regulation of Adrenocortical Function

Lefebvre¹,

Contesse

Delarue

et al. 1998

Horm Metab Res

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Serotonin (5-HT) plays a pivotal role in the regulation of the hypothalamo-pituitary-adrenal axis. In particular, 5-HT is involved in the stimulation of ACTH secretion during stress. Recent data indicate that, at the adrenal level, 5-HT acts as a local regulator of corticosteroid secretion. The presence of 5-HT in the adrenal gland has been demonstrated immunohistochemically and biochemically in various species including frog, mouse, rat and human. In the mouse, 5-HT has been detected in nerve fibers while, in the frog and rat, 5-HT appears to be sequestered in chromaffin cells. In man, 5-HT is stored in perivascular mast cells. In vivo and in vitro studies have shown that 5-HT stimulates mineralo- and glucocorticoid secretion from adrenal cells. In rat, the type of receptor involved in the corticotropic effect of 5-HT is still controversial. In the frog and the human, the effect of 5-HT on the adrenal cortex is mediated through a 5-HT4 receptor subtype positively coupled to adenylyl cyclase and calcium influx. Clinical studies indicate that 5-HT4 receptor agonists stimulate aldosterone secretion in healthy volunteers and in patients with aldosterone disorders. The 5-HT4 receptor agonist cisapride and angiotensin II exert additive effects on aldosterone secretion. In contrast, cisapride has no influence on ACTH-induced aldosterone release. Collectively, these findings suggest that intra-adrenal 5-HT stimulates the secretory activity of adrenocortical cells through a paracrine mode of communication involving a 5-HT4 receptor type. Serotonergic control of corticosteroid production may be involved in the physiological control of the activity of the adrenal cortex, in particular during inflammatory stress. 5-HT may also be implicated in the pathophysiology of aldosterone disorders.

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“…8-0H-DPAT (5-HT 1 A receptor agonist) and DOl (5-HT 2 receptor agonist) are generally considered as stimulators of PRL secretion (2,9,34). Our results evidenced a differential age-change of their role during prepubertal development.…”

Section: Effects Of 5-ht 1 a 5-htmentioning

confidence: 50%

Interactions between serotoninergic and aminoacidergic pathways in the control of PRL secretion in prepubertal male rats

Pinilla

González

Tena‐Sempere

et al. 2001

J. Physiol. Biochem.

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Prolactin secretion is controlled by the hypothalamus through different neurotransmitters which interact with multiple receptor subtypes. The discovery of different families of receptors for serotonin (5-HT1-5-HT7) and excitatory aminoacids (NMDA, KA, AMPA and metabotropic receptors) ilustrates the complexity of this regulation. Moreover, in the rat the role of different neurotransmitters changes during pubertal development. Present experiments were carried out to analyse the interactions between AMPA and serotoninergic receptors in the control of prolactin secretion in prepubertal male rats. For this purpose, 16 and 23-day old male rats were treated with 5-hydroxytryptophan (5-HTP, precursor of serotonin synthesis) plus fluoxetine (blocker of serotonin reuptake), 8-OH-DPAT (agonist of 5-HT1A receptors), DOI and alpha-Me-5-HT (agonists of 5-HT2 receptors), 1-phenylbiguanide (agonist of 5-HT3 receptors) alone or in combination with AMPA (agonist of AMPA receptors). The results obtained indicate that: (a) activation of 5-HT1A receptors stimulated PRL secretion on day 16 and inhibited it on day 23; activation of 5-HT2 receptors stimulated PRL secretion on days 16 and 23, whereas activation of 5-HT3 receptors inhibited PRL release only on day 23; (b) activation of AMPA receptors inhibited PRL secretion on day 23, but not on day 16 and (c) a cross-talk is apparent between 5-HT2 and AMPA receptors in the regulation of PRL secretion, the stimulatory effect of DOI being blocked by AMPA.

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Central Stimulation of Renin Secretion through Serotonergic, Noncardiovascular Mechanisms

Cited by 13 publications

References 18 publications

Effect of the Serotonin 5-HT<sub>4</sub> Receptor Agonist Cisapride on Aldosterone Secretion in Corticotropic Insufficiency and Primary Hyperaldosteronism

Effect of the Serotonin 5-HT<sub>4</sub> Receptor Agonist Cisapride on Aldosterone Secretion in Corticotropic Insufficiency and Primary Hyperaldosteronism

Serotonergic Regulation of Adrenocortical Function

Interactions between serotoninergic and aminoacidergic pathways in the control of PRL secretion in prepubertal male rats

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