title: Brain α4β2 nicotinic acetylcholine receptors are involved in the secretion of noradrenaline and adrenaline from adrenal medulla in rats.
abstract: 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-β-erythroidine (a selective antagonist of α4β2 nicotinic acetylcholine receptors) (100 and 300nmol/animal, i.c.v.), while methyllycaconitine (a selective antagonist of α7 nicotinic acetylcholine receptors) (100 and 300nmol/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 5μmol/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 5μmol/animal, i.c.v.) had no effect. Furthermore, the RJR-2403 (5μmol/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.
authors.affiliation: Department of Pharmacology, School of Medicine, Kochi University, Nankoku, Kochi 783-8505, Japan. shimizu@kochi-u.ac.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Takashi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokotani
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood; D004837:Epinephrine / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology
chemical_list: D002395:Catecholamines; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D009638:Norepinephrine; D004837:Epinephrine