Muscarinic cholinergic receptors in canine adrenal gland

Abstract

Muscarinic cholinergic receptor stimulation has been reported to modulate adrenal catecholamine and steroid secretion and influence medullary vascular tone. The present study was undertaken to localize and characterize muscarinic cholinergic receptor binding sites in canine adrenal medulla and cortex. Binding studies using semipurified membranes demonstrated specific, saturable binding of L-[benzilic-4,4'-3H(N)]-quinuclidinyl benzilate ([3H]QNB) in medulla, with a dissociation constant (KD) equal to 152 pM and estimated maximal binding sites (Bmax) equal to 179 fmol/mg protein. Displacement of [3H]QNB by cholinergic agents in order of decreasing potency was atropine, pirenzepine, oxotremorine, pilocarpine, and carbamylcholine, suggesting the receptor was M1 subtype, similar to sympathetic ganglion muscarinic receptors. Autoradiographic imaging studies demonstrated highly specific, homogeneous binding throughout the medulla. No specific binding was found in adrenal cortex. These results suggest that muscarinic effects on blood flow may be neurally mediated, rather than the result of stimulation of vascular muscarinic receptors. In medulla, muscarinic receptors are evenly distributed and modulate catecholamine secretion in all cells rather than subpopulations of cells as in other species. Absence of [3H]QNB binding in cortex argues against muscarinic receptor modulation of cortical steroid secretion.