NICOTINIC RECEPTORS AUTONOMIC GANGLIA AND ADRENAL GLAND

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DESCRIPTION(Adapted from applicant's abstract): The objectives of the studies described in this application are to compare the subunit composition, pharmacological profile and regulation of neuronal nicotinic receptors in rat autonomic ganglia and adrenal glad. In addition to their intrinsic physiological importance, these neuronal tissues are affected by nicotine and thus provide excellent model systems in which to explore the relationships between receptor subunit composition, pharmacology and regulation of nicotinic receptors by acute and chronic exposure to nicotine. Until recently it would have been difficult to develop a full understanding of the subunit composition, comparative pharmacology and regulation of native nicotinic receptor subtypes in mammalian neuronal tissues because of limitations in the methods and tools available to reliably measure and identify these receptor subtypes in native tissues. We believe these constraints can now be overcome. In the studies described here we will use the high affinity ligands [3H]epibatidine, [125I]epibatidine and [125I]A85380 to label these receptors in autonomic ganglia and adrenal gland and subunit-specific antibodies to determine the subunit composition of the receptors in each tissue. We will then examine the function of these receptor subtypes and determine how acute and chronic exposure to nicotine affects each. Thus, the specific aims of these studies are to: 1) compare the subunit composition of the receptors in these autonomic ganglia and adrenal gland; 2) compare the pharmacological characteristics of the different subtypes of these native receptors; 3) compare the pharmacological characteristics of the native receptors in these tissues with those in defined receptor subtypes stably expressed in mammalian cells; 4) examine the function and pharmacology of the nicotinic receptors in the rat adrenal gland in vivo; and 5) examine the regulation of the function and density of the nicotinic receptors in rat adrenal gland and ganglia after acute and chronic exposure to nicotine.