<i>IN VIVO</i> AND <i>IN VITRO</i> STUDIES ON THE EFFECT OF METOCLOPRAMIDE ON ALDOSTERONE SECRETION

Edwards, C. R. W.; Al-Dujaili, Emad A S; Boscaro, Marco; Quyyumi, Shahed; Miall, P; Rees, Lesley

doi:10.1111/j.1365-2265.1980.tb01021.x

Cited by 68 publications

(27 citation statements)

References 9 publications

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“…The changes in PRA following i.c.v. dopamine or metoclopramide administration in the present study are quite different from other reports, 6 l3> l4 in which i.v. administration of dopamine or metoclopramide did not alter the PRA in human subjects.…”

Section: Discussioncontrasting

confidence: 56%

“…Although many investigators have shown that peripherally infused dopamine or metoclopramide alters aldosterone secretion in humans, 3 ' ' 3i l4-M dopamine reportedly had no effect on aldosterone output of bovine adrenal cells, nor did it block the aldosterone response to ANG II in superfused rat adrenal cells. 6 In addition to the present observation, studies on Na-depleted or Na-replete sheep showed that dopamine or metoclopramide had basically no direct effect on the adrenal. 8 ' 10 Furthermore, metoclopramide had no effect on plasma corticosteroid levels in humans, 31314 but it stimulated corticosteroid secretion in sheep.…”

Section: Discussionmentioning

confidence: 84%

“…17 In addition to the finding that metoclopramide increases aldosterone secretion in vivo, 3 evidence has been provided to show that dopamine blocks metoclopramide-stimulated aldosterone secretion in a dose-dependent fashion. 6 ' 13t 18 Therefore, it is reasonable to conclude that the aldosterone response to metoclopramide is mediated by metoclopramide's antagonist activity at the level of the dopamine receptor.…”

Section: Discussionmentioning

confidence: 99%

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Central dopaminergic regulation of aldosterone secretion in sheep.

Huang¹,

Malvin²,

Lee³

et al. 1987

Hypertension

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SUMMARY Central dopaminergic mechanisms involved in the regulation of plasma aldosterone concentration were investigated in 16 conscious sheep following Na depletion with intramuscularly administered furosemide. Intracerebroventricular infusion of dopamine (20 /xg/min) decreased plasma aldosterone significantly to 52 ± 8% of basal level and increased plasma renin activity (PRA) significantly to 172 ± 25% of basal level in this animal model. In addition, intracerebroventricular infusion of the dopamine antagonist metoclopramide (20 /ug/min) in artificial cerebrospinal fluid vehicle significantly increased aldosterone levels to 144 ±14% of basal level and decreased PRA to 62 ± 5% of basal value. Neither intracerebroventricular infusion of the vehicle nor intravenous infusions of metoclopramide or dopamine at the same doses changed aldosterone or PRA levels. Intracerebroventricular bolus injections of metoclopramide (20 /xg/kg in 0.4 ml of vehicle) were also effective, increasing aldosterone levels to 266 ± 22% of basal level and decreasing PRA to 70 ± 12% of basal level. Intravenous bolus injections of the same dose of metoclopramide were ineffective. Dopamine was infused intracerebroventricularly into two uniadrenalectomized sheep with the remaining adrenal transplanted to the neck. Aldosterone levels were decreased to 49 ± 10% of basal level, and PRA was increased to 157 ±10% of basal value. None of the infusions or injections changed arterial or intracranial pressure, or plasma K, Na, and cortisol levels. These data indicate that endogenous or exogenous dopamine may act on central dopamine receptors to decrease plasma aldosterone concentration by an unknown humoral mechanism. The known aldosterone regulators, plasma Na, K, angiotensin II, and adrenocorticotropic hormone, are not involved in the regulation. (Hypertension 10: 157-163, 1987) KEY WORDS • brain dopaminergic pathway transplant • metoclopramide aldosterone secretion adrenal I N earlier studies, 1 we showed that centrally administered dopamine inhibited the release of aldosterone, an effect that is independent of changes in plasma Na, K, adrenocorticotropic hormone (ACTH), and angiotensin II (ANG II) levels. However, these studies did not clarify whether the effects of centrally infused dopamine were due to central or to peripheral actions or the mechanism by which central dopamine might suppress aldosterone secreFrom the

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Central dopaminergic regulation of aldosterone secretion in sheep.

Huang¹,

Malvin²,

Lee³

et al. 1987

Hypertension

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“…From invivo and in-vitro studies, there is indirect evidence that dopamine tonically inhibits aldosterone secretion (2 -I1) and blunts angiotensin II-stimulated aldosterone secretion (31)(32)(33)(34)(35). Two different types of dopaminergic receptors have been identified in the rat adrenal cortex (36): the DA2 type, associated with inhibition of adenylate cyclase and of aldosterone secretion, and the DA1 type, associated with activation of adenylate cyclase and increased cAMP levels, the physiological roles for which are as yet unknown.…”

Section: Discussionmentioning

confidence: 99%

Dopaminergic Regulation of Aldosterone Secretion in Primary Aldosteronism: A Clinical Study.

Rossi¹,

Zanin²,

Toni³

et al. 1994

Hypertens Res

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To assess the role of dopaminergic inhibition of aldosterone secretion in primary aldosteronism (PA) we studied the effect of dopaminergic DA2 blockade and stimulation in a series of consecutive cases of PA, and of primary hypertension (PH) as controls. Thirteen patients with confirmed PA (11 adenoma, 2 idiopathic hyperaldosteronism) and 8 primary hypertensive subjects (PH) were studied while on a 100 mmol/day sodium diet. Patients with aldosterone-producing adenoma were studied before, 1-2 wk after, and 6 months after surgery. The DA2-antagonist metoclopramide (10 mg i.v.) and the DA2-agonist dihydroergotoxine (6 ,ug/Kg b.w. i.v.) were administered on different days. The effect of the latter on adrenal vein aldosterone and cortisol levels was also studied in selected cases. Plasma aldosterone, prolactin, cortisol, renin activity, free catecholamines, ACTH, Na+ , K+ , heart rate, and blood pressure were measured before and repeatedly after administration of each drug. In both groups, metoclopramide significantly increased aldosterone, prolactin, and cortisol (p < 0.01), slightly decreased K+ , and did not change the other variables. In PA patients, the aldosterone output was significantly (p < 0.05) greater than in PH, and fell after surgery. There was no difference, however, in responsiveness to metoclopramide between PA and control patients. Dihydroergotoxine significantly decreased plasma prolactin and aldosterone levels and adrenal vein aldosterone in patients with PH. In contrast, despite a similar decrease in prolactin, in PA a significant (p < 0.05) increase in aldosterone was seen, both peripherally and in adrenal vein blood. Thus, in PA: 1) the response to DA2 blockade is qualitatively normal but quantitatively enhanced; 2) this enhancement disappears after removal of the adenoma and thus appears related to increased aldosterone-secreting tissue rather than to enhanced responsiveness; 3) the response stimulation by dihydroergotoxine is paradoxical in PA, and may be mediated through ACTH stimulation. (Hypertens Res 1994; 17: 105-115)

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“…Although in recent years the emphasis in pathways to aldosterone secretion has been via stimuli to CYP11B2 transcription, earlier literature showed that many effects, including postural changes and those of dopamine, occur within minutes-namely too fast for a transcriptional response. [34][35][36] Finally, the recognition of NEFM as a selective marker of ZG-like APAs gave us the opportunity for testing whether the ZF-like phenotype might be a consequence of its commonest genotype, namely the KCNJ5 mutation, rather than from arising in ZF cells, where KCNJ5 expression is scarce. The disappearance of NEFM from KCNJ5-transfected cells would favor the first of these alternatives and indeed explain why D1R remains on the surface of ZF-like APA cells.…”

Section: Discussionmentioning

confidence: 99%

NEFM (Neurofilament Medium) Polypeptide, a Marker for Zona Glomerulosa Cells in Human Adrenal, Inhibits D1R (Dopamine D1 Receptor)–Mediated Secretion of Aldosterone

et al. 2017

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A ldosterone-producing adenomas (APAs) are responsible for ≈5% of hypertension and are probably its most common curable cause. 1 The heterogeneity of these tumors has been highlighted by the landmark discovery of somatic mutations of KCNJ5, followed by others in ATP2B3, ATP1A1, CACNA1D, and CTNNB1. [2][3][4][5] The genotype and histological features delineate 2 overlapping APA subtypes: the common, large KCNJ5 mutant APAs histology is usually similar to cortisol-producing zona fasciculata (ZF) and smaller APAs with other mutations are mainly composed of zona glomerulosa (ZG)-like compact, lipid-depleted cells.The 2 subtypes present other phenotypic differences: for instance, elevated secretion from an APA of hybrid steroids 18-hydroxycortisol and 18-oxocortisol could be considered a fingerprint of KCNJ5 mutation.6 Further differences about the response to aldosterone secretagogues, such as angiotensin II or metoclopramide, have been previously reported. 7,8 Dopamine is one of the main regulators of aldosterone secretion. 9 The 5 known dopamine receptors belong to the G-protein-coupled receptor superfamily and are classified into 2 major subgroups (D1-like and D2-like) according to their structure and opposite action on cAMP production. Activation of the D1-like subfamily members (D1R and D5R) causes an increase of intracellular cAMP levels. The D2-like subfamily includes D2R, D3R, and D4R receptors; their transduction of signal causes a reduction of cAMP production. 10In human adrenal, most attention has been paid to the D2R subtype. This is expressed in normal ZG and mediates dopamine inhibition of aldosterone response to angiotensin II (but not to adrenocorticotropic hormone or potassium) 11,12 and tonic

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IN VIVO AND IN VITRO STUDIES ON THE EFFECT OF METOCLOPRAMIDE ON ALDOSTERONE SECRETION

Cited by 68 publications

References 9 publications

Central dopaminergic regulation of aldosterone secretion in sheep.

Central dopaminergic regulation of aldosterone secretion in sheep.

Dopaminergic Regulation of Aldosterone Secretion in Primary Aldosteronism: A Clinical Study.

NEFM (Neurofilament Medium) Polypeptide, a Marker for Zona Glomerulosa Cells in Human Adrenal, Inhibits D1R (Dopamine D1 Receptor)–Mediated Secretion of Aldosterone

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