Central serotonergic stimulation of aldosterone secretion.

Shenker, Yoram; Gross, Milton D.; Grekin, Roger J.

doi:10.1172/jci112128

Cited by 37 publications

(16 citation statements)

References 46 publications

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“…5-HTP caused a significant and prompt increase in aldosterone levels without any increase in PRA in keeping with previous studies in man that the release of aldosterone by 5-HTP is independent of activation of the renin angiotensin system [16,17]. This effect on aldosterone may be due to direct stimulation of the adrenal cortex [18] or may be mediated by central 5-HT pathways as 5-HTP can cross the blood brain barrier [16].…”

Section: Discussionsupporting

confidence: 89%

“…This effect on aldosterone may be due to direct stimulation of the adrenal cortex [18] or may be mediated by central 5-HT pathways as 5-HTP can cross the blood brain barrier [16]. 5-HTP also stimulates the release of other hormones such as prolactin, ACTH, growth hormone and cortisol, providing further evidence that it can act centrally [19,20].…”

Section: Discussionmentioning

confidence: 92%

“…

1 The effects of 1 h intravenous infusions of equimolar amounts of two putative 5-hydroxytryptamine (5-HT) renal prodrugs, 5-hydroxy-L-tryptophan (5-HTP, 10 ,ug kg-1 min-') and y-L-glutamyl-5-hydroxy-L-tryptophan 16.6 jig kg-1 min-1) were examined in five healthy male volunteers in a randomised, placebocontrolled, cross-over study. 2 Both compounds increased urinary excretion of 5-HT and there was greater extrarenal formation of 5-HT following 5-HTP administration than after glu-5-HTP.

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confidence: 99%

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A comparison of the effects of two putative 5‐hydroxytryptamine renal prodrugs in normal man.

Freestone

Samson

et al. 1993

Brit J Clinical Pharma

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1. The effects of 1 h intravenous infusions of equimolar amounts of two putative 5‐hydroxytryptamine (5‐HT) renal prodrugs, 5‐hydroxy‐L‐ tryptophan (5‐HTP, 10 micrograms kg‐1 min‐1) and gamma‐L‐glutamyl‐5‐ hydroxy‐L‐tryptophan (glu‐5‐HTP, 16.6 micrograms kg‐1 min‐1) were examined in five healthy male volunteers in a randomised, placebo‐ controlled, cross‐over study. 2. Both compounds increased urinary excretion of 5‐HT and there was greater extra‐renal formation of 5‐HT following 5‐HTP administration than after glu‐5‐HTP. 3. Glu‐5‐HTP was significantly antinatriuretic. 5‐HTP reduced mean urinary sodium excretion but this effect was not statistically significant. 4. 5‐HTP, but not glu‐5‐HTP, significantly increased plasma aldosterone. There was no increase in plasma renin activity with either compound. 5. There were no significant changes in pulse rate or blood pressure. Two subjects complained of nausea at the end of 5‐HTP infusion but none had any adverse reactions with glu‐5‐HTP. 6. The results of this study suggest that both prodrugs generate 5‐HT in man and that glu‐5‐HTP is antinatriuretic. The glutamyl derivative may have greater renal specificity than 5‐HTP and, as a result, causes less systemic side effects.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 92%

“…

…”

mentioning

confidence: 99%

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A comparison of the effects of two putative 5‐hydroxytryptamine renal prodrugs in normal man.

Freestone

Samson

et al. 1993

Brit J Clinical Pharma

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“…These results are consistent with significant inhibition of renal LAAD. ing administration of 5-HTP and to increase the stimulatory effect of 5-HTP on aldosterone suggesting that central 5-HT pathways are involved in the stimulation of aldosterone induced by administration of 5-HTP [17,21]. In the present study, however, carbidopa attenuated the increase in aldosterone secretion following glu-5-HTP.…”

Section: Discussioncontrasting

confidence: 66%

The antinatriuretic action of gamma‐L‐glutamyl‐5‐hydroxy‐L‐tryptophan is dependent on its decarboxylation to 5‐hydroxytryptamine in normal man.

Freestone

Samson

et al. 1994

Brit J Clinical Pharma

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1 The effects of inhibition of peripheral aromatic L-amino acid decarboxylase during infusion of the relatively renally selective 5-hydroxytryptamine (5-HT) prodrug, y-L-glutamyl-5-hydroxy-L-tryptophan , were examined in eight healthy male subjects in a randomised, placebo-controlled, cross-over study. 2 Each subject received oral carbidopa (100 mg) or placebo followed, 1 h later, by a 60 min intravenous infusion of glu-5-HTP (16.6 jg kg-1 min-') or placebo.3 After administration of glu-5-HTP, cumulative urinary excretion of 5-HT was 430-fold greater than that after placebo, and was associated with a period of sodium retention. 4 Pretreatment with carbidopa substantially attenuated the increase in 5-HT excretion after glu-5-HTP and abolished its antinatriuretic effect. 5 These results are in keeping with the proposition that the antinatriuretic action of glu-5-HTP is dependent on its decarboxylation to 5-HT. 5-hydroxytryptamine sodium excretion ale y-L-glutamyl-5-hydroxy-L-tryptophan dosteroneThe first step in the biosynthesis of 5-hydroxytryptamine (5-HT; serotonin) involves the hydroxylation of the essential amino acid L-tryptophan to 5-hydroxytryptophan (5-HTP) by the enzyme tryptophan-5-hydroxylase. 5-HTP is decarboxylated by aromatic L-amino acid decarboxylase (LAAD) to 5-HT. The latter is degraded primarily by monoamine oxidase to produce 5-hydroxyindoleacetic acid (5-HIAA) which is the major catabolic and excretory product of 5-HT metabolism. All these enzymes are present in renal tissue, suggesting that the kidney might have the capacity to synthesise and degrade 5-HT locally [1,2]. The enzyme y-glutamyl transferase (yGT) is also present in high concentrations and the kidney is highly active in the uptake and metabolism of y-glutamyl derivatives of amino acids [3,4]. We previously demonstrated marked increases in urinary 5-HT excretion after infusion of the 5-HT prodrug, y-L-glutamyl-5-hydroxy-L-tryptophan (glu-5-HTP), in keeping with intrarenal synthesis of 5-HT following the conversion of glu-5-HTP to 5-HTP by yGT and its subsequent decarboxylation by renal LAAD to 5-HT [5,6]. Glu-5-HTP was relatively more selective for the kidney than 5-HTP. It reduced urinary sodium excretion without significant alterations in renal haemodynamics and this was due, presumably, to intrarenally generated 5-HT.The present study was designed to investigate whether carbidopa, a peripheral inhibitor of LAAD [7], blocks the formation of 5-HT from glu-5-HTP and interferes with the actions of glu-5-HTP in normal volunteers. MethodsEight male volunteers, age range 18-39 years (mean 28 years) and weighing 59.9-80.9 kg (mean 69.0 kg),

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“…Thus, these findings indicate a role for 5-HT in the mediation of MDMA-induced HPA axis stimulation in humans but little or no role for NE. Additionally, MDMA releases 5-HT from peripheral non-neuronal tissues directly into the blood plasma [49] and 5-HT has been shown to directly stimulate aldosterone secretion by glomerulosa cells [50]. …”

Section: Discussionmentioning

confidence: 99%

Acute Effects of 3,4-Methylenedioxymethamphetamine and Methylphenidate on Circulating Steroid Levels in Healthy Subjects

et al. 2014

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3,4-Methylenedioxymethamphetamine (MDMA, ‘ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-hour plasma steroid profiles. 16 healthy subjects (8 men, 8 women) were treated with single doses of MDMA (125 mg), methylphenidate (60 mg), MDMA + methylphenidate, and placebo on 4 separate days using a cross-over study design. Cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycorticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were repeatedly measured up to 24 h using liquid chromatography-tandem mass spectroscopy. MDMA significantly increased the plasma concentrations of cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone and also tended to moderately increase aldosterone levels compared with placebo. MDMA also increased the sum of cortisol + cortisone and the cortisol/cortisone ratio, consistent with an increase in glucocorticoid production. MDMA did not alter the levels of cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate did not affect any of the steroid concentrations, and it did not change the effects of MDMA on circulating steroids. In summary, the serotonin releaser MDMA has acute effects on circulating steroids. These effects are not observed after stimulation of the dopamine and norepinephrine systems with methylphenidate. The present findings support the view that serotonin rather than dopamine and norepinephrine mediates the acute pharmacologically induced stimulation of the hypothalamic-pituitary-adrenal axis in the absence of other stressors.

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Central serotonergic stimulation of aldosterone secretion.

Cited by 37 publications

References 46 publications

A comparison of the effects of two putative 5‐hydroxytryptamine renal prodrugs in normal man.

A comparison of the effects of two putative 5‐hydroxytryptamine renal prodrugs in normal man.

The antinatriuretic action of gamma‐L‐glutamyl‐5‐hydroxy‐L‐tryptophan is dependent on its decarboxylation to 5‐hydroxytryptamine in normal man.

Acute Effects of 3,4-Methylenedioxymethamphetamine and Methylphenidate on Circulating Steroid Levels in Healthy Subjects

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