Further evidence for nicotinic and muscarinic receptors and their interaction in dog adrenal medulla

Abstract

Isolated adrenal glands of dogs were perfused through the adrenolumbar vein with Krebs-Ringer phosphate solution. Nicotine or acetylcholine (Ach) significantly increased the proportion of norepinephrine in the effluent whereas muscarine did not alter the relative proportions of epinephrine and norepinephrine. d-Tubocurarine and hexamethonium (C6) inhibited the response to nicotine completely but scarcely affected the response to Ach and significantly potentiated the response to muscarine. Atropine inhibited the response to muscarine completely, that to Ach partially and that to nicotine slightly. Preinfusion of physostigmine potentiated the secretory response to Ach but not that to nicotine and muscarine. When nicotine and muscarine were infused simultaneously, catecholamine (CA) release was greater than the sum of the responses to nicotine and muscarine separately. Continuous infusion of nicotine for 60 min caused block of the adrenal medulla but potentiated CA release in response to Ach and more especially to muscarine. This potentiated release of CA was completely blocked by preinfusion of atropine. Continuous infusion of muscarine for 60 min also blocked CA release and significantly potentiated the response to nicotine, but slightly inhibited the response to Ach. These potentiated and inhibited responses were also completely blocked by preinfusion of d-tubocurarine of C6. On the contrary, during the blockade phase caused by Ach (in combination with physostigmine), nicotine of muscarine did not cause release of CA. In addition, the continuous infusion of nicotine plus muscarinic receptors for acetylcholine in the adrenal medulla and that cholinergic transmission is possible via both mechanisms in isolated adrenal glands. When one type of receptors is blocked by continuous contact with an agonist or by d-tubocurarine or C6, the sensitivity of the other type is increased; inactivation of the one is thus compensated by the increased response due to potentiation of the other.