Effects of sulfhydryl modification on adrenal nicotinic acetylcholine receptors - Disulfide integrity is not essential for activation

The importance of disulfide bridges in muscle nicotinic receptors is well e stablished; however, for neuronal nicotinic receptors, the effects of sulfh ydryl modification are less definitive. In these studies the effects of tre atment with the mild reducing agent, dithiothreitol, on adrenal nicotinic r eceptors are described. We have found that following dithiothreitol treatme nt, adrenal chromaffin cells retained the ability to be stimulated by a var iety of nicotinic receptor agonists including nicotine, acetylcholine, cyti sine, epibatidine, and bromoacetylcholine. However, with dithiothreitol tre atment, changes in apparent affinities were seen with two agonists, epibati dine and bromoacetylcholine. These effects of dithiothreitol on apparent af finities were concentration-dependent and reversible upon treatment with an oxidizing agent. Dithiothreitol treatment also produced effects on secreti on that were independent of nicotinic receptor activation. Our results are unlike those in other tissues containing nicotinic receptors and suggest th at subunit composition of nicotinic receptors influences the functional out come of sulfhydryl modification. (C) 2000 Elsevier Science Inc. All rights reserved.