Brain α4β2 nicotinic acetylcholine receptors are involved in the secretion of noradrenaline and adrenaline from adrenal medulla in rats

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 10 nmol/animal, i.c.v.) and (−)-nicotine (250 and 500 nmol/animal, i.c.v.) both elevated plasma noradrenaline and adrenaline (adrenaline > noradrenaline) but the former was more efficient than the latter. The (±)-epibatidine (5 nmol/animal, i.c.v.)-induced elevation of plasma catecholamines was reduced by dihydro-β-erythroidine (a selective antagonist of α4β2 nicotinic acetylcholine receptors) (100 and 300 nmol/animal, i.c.v.), while methyllycaconitine (a selective antagonist of α7 nicotinic acetylcholine receptors) (100 and 300 nmol/animal, i.c.v.) had no effect on the (±)-epibatidine-induced responses. RJR-2403 (a selective agonist of α4β2 nicotinic acetylcholine receptors) (2.5 and 5 μmol/animal, i.c.v.) elevated plasma noradrenaline and adrenaline (adrenaline > noradrenaline), while PNU-282987 (a selective agonist of α7 nicotinic acetylcholine receptors) (2.5 and 5 μmol/animal, i.c.v.) had no effect. Furthermore, the RJR-2403 (5 μmol/animal, i.c.v.)-induced responses were abolished by acute bilateral adrenalectomy. Immunohistochemical procedures demonstrated the expression of α4 and β2 nicotinic acetylcholine receptor subunits on the spinally projecting hypothalamic paraventricular neurons. Taken together, brain α4β2 nicotinic acetylcholine receptors seem to be involved in the secretion of noradrenaline and adrenaline from adrenal medulla in rats.