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 established; however, for neuronal nicotinic receptors, the effects of sulfhydryl modification are less definitive. In these studies the effects of treatment with the mild reducing agent, dithiothreitol, on adrenal nicotinic receptors are described. We have found that following dithiothreitol treatment, adrenal chromaffin cells retained the ability to be stimulated by a variety of nicotinic receptor agonists including nicotine, acetylcholine, cytisine, epibatidine, and bromoacetylcholine. However, with dithiothreitol treatment, changes in apparent affinities were seen with two agonists, epibatidine and bromoacetylcholine. These effects of dithiothreitol on apparent affinities were concentration-dependent and reversible upon treatment with an oxidizing agent. Dithiothreitol treatment also produced effects on secretion that were independent of nicotinic receptor activation. Our results are unlike those in other tissues containing nicotinic receptors and suggest that subunit composition of nicotinic receptors influences the functional outcome of sulfhydryl modification.
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Division of Pharmacology, The Ohio State University, College of Pharmacy, Columbus 43210, USA.
Wenger
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McKay
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D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D002395:Catecholamines; D004220:Disulfides; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D004229:Dithiothreitol