The effect of neostigmine on metoclopramide-induced aldosterone secretion after the administration of muscarinic antagonists in man
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Summary
In this study the effects of neostigmine on metoclopramide-induced aldosterone secretion were examined in the presence of a relatively selective M1-antagonist, pirenzepine and of a non-selective muscarinic antagonist, atropine.
Six normal male volunteers received metoclopramide, 10 mg i.v. on three different occasions, each study day being preceded by a day in which the intake of sodium and potassium was limited. The dosing was either metoclopramide alone or combined with either neostigmine and pirenzepine or with neostigmine and atropine.
Serum aldosterone increased significantly with all three regimens. The highest levels were attained with the metoclopramide/neostigmine/prienzepine regimen and those were significantly higher than those after metoclopramide alone and also, from 45 min onwards, from those after the metoclopramide/neostigmine/atropine regimen.
The results of this investigation suggest that the metoclopramide-induced aldosterone secretion in humans is augmented by an accumulation of acetylcholine at the nerve-zona glomerulosa junctions and that the receptors mediating aldosterone secretion are of the M2-subclass of muscarinic receptors.
Key words
neostigmine metoclopramide aldosterone secretion neostigmine pirenzepine atropine zona glomerulosa M2-muscarinic receptorPreview
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References
- Aguilera G, Mendelsohn FAO, Catt KJ (1984) Dopaminergic regulation of aldosterone secretion. In: Martini L, Ganong WF (eds) Frontiers in neuroendocrinology, vol8. Raven Press, New York, pp 265–293Google Scholar
- Dupont AG, Vanderniepen P, Smitz JJ, Six RO (1985) Stimulation of aldosterone secretion by metoclopramide is not affected by chronic converting enzyme inhibition. Eur J Clin Pharmacol 29: 207–210Google Scholar
- Eisner M (1986) Gastrointestinal effects of metoclopramide in man: In vitro experiments with human smooth muscle preparations. Br Med J 4: 679–680Google Scholar
- Hammer R, Berrie CP, Birdsall NJM, Burgen ASV, Hulme EC (1980) Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature 283: 90–92Google Scholar
- Hay AM (1977) Pharmacological analysis of the effects of metoclopramide on the guinea pig isolated stomach. Gastroenterology 72: 864–869Google Scholar
- Jungman E, Althoff PH, Hermann GT, Schoffling K (1985) No effect of pizotifen, a serotonin antagonist and of pirenzepine, a muscarinic receptor blocker, on aldosterone stimulation by metoclopramide, hyperkalaemia and furosemide. J Hypertens 3: 412–413Google Scholar
- Sommers De K, Meyer EC, van Wyk M, de Villiers LS (1988) Aldosterone response to metoclopramide is mediated through the autonomic nervous system in man. Eur J Clin Pharmacol 33: 609–612Google Scholar
- Sommers De K, Meyer EC, van Wyk M (1989) Effect of neostigmine on metoclopramide-induced aldosterone secretion in man. Eur J Clin Pharmacol 36: 411–413Google Scholar
- Watson M, Vickroy TW, Roeske WR, Yamamura HI (1984) Subclassification of muscarinic receptors based upon the selective antagonist pirenzepine. Trends Pharmacol Sci 6 [Suppl]: 9–11Google Scholar