Brain @a4@b2 nicotinic acetylcholine receptors are involved in the secretion of noradrenaline and adrenaline from adrenal medulla in rats

Eur J Pharmacol 654(3):8 (2011) PMID 21237150

Recently, we reported that intracerebroventricularly (i.c.v.) administered (+/-)-epibatidine (a non-selective agonist of nicotinic acetylcholine receptors) elevates plasma noradrenaline and adrenaline through brain nicotinic acetylcholine receptor-mediated mechanisms in rats. In the present study, we characterized the receptors involved in these responses using selective agonists and antagonists of nicotinic acetylcholine receptor subtypes in anesthetized rats. (+/-)-Epibatidine (5 and 10nmol/animal, i.c.v.) and (-)-nicotine (250 and 500nmol/animal, i.c.v.) both elevated plasma noradrenaline and adrenaline (adrenaline>noradrenaline) but the former was more efficient than the latter. The (+/-)-epibatidine (5nmol/animal, i.c.v.)-induced elevation of plasma catecholamines was reduced by dihydro-@b-erythroidine (a selective antagonist of @a4@b2 nicotinic acetylcholine receptors) (100 and 300nmol/animal, i.c.v.), while methyllycaconitine (a selective antagonist of @a7 nicotinic acetylcholine receptors) (100 and 300nmol/animal, i.c.v.) had no effect on the (+/-)-epibatidine-induced responses. RJR-2403 (a selective agonist of @a4@b2 nicotinic acetylcholine receptors) (2.5 and 5@mmol/animal, i.c.v.) elevated plasma noradrenaline and adrenaline (adrenaline>noradrenaline), while PNU-282987 (a selective agonist of @a7 nicotinic acetylcholine receptors) (2.5 and 5@mmol/animal, i.c.v.) had no effect. Furthermore, the RJR-2403 (5@mmol/animal, i.c.v.)-induced responses were abolished by acute bilateral adrenalectomy. Immunohistochemical procedures demonstrated the expression of @a4 and @b2 nicotinic acetylcholine receptor subunits on the spinally projecting hypothalamic paraventricular neurons. Taken together, brain @a4@b2 nicotinic acetylcholine receptors seem to be involved in the secretion of noradrenaline and adrenaline from adrenal medulla in rats.

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