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The Nicotinic Receptor in the Rat Pineal Gland Is an 34 Subtype

Departments of Pharmacology (S.C.H., Y.X., R.P.Y., B.B.W., K.J.K.) and Physiology & Biophysics (S.V.), Georgetown University School of Medicine, Washington, DC; and Department of Pharmacology, Howard University College of Medicine, Washington, DC (M.I.D.-G.)

The rat pineal gland contains a high density of neuronal nicotinic acetylcholine receptors (nAChRs). We characterized the pharmacology of the binding sites and function of these receptors, measured the nAChR subunit mRNA, and used subunit-specific antibodies to establish the receptor subtype as defined by subunit composition. In ligand binding studies, [³H]epibatidine ([³H]EB) binds with an affinity of 100 pM to nAChRs in the pineal gland, and the density of these sites is 5 times that in rat cerebral cortex. The affinities of nicotinic drugs for binding sites in the pineal gland are similar to those at 34 nAChRs heterologously expressed in human embryonic kidney 293 cells. In functional studies, the potencies and efficacies of nicotinic drugs to activate or block whole-cell currents in dissociated pinealocytes match closely their potencies and efficacies to activate or block ⁸⁶Rb⁺ efflux in the cells expressing heterologous 34 nAChRs. Measurements of mRNA indicated the presence of transcripts for 3, 2, and 4 nAChR subunits but not those for 2, 4, 5, 6, 7, or 3 subunits. Immunoprecipitation with subunit-specific antibodies showed that virtually all [³H]EB-labeled nAChRs contained 3 and 4 subunits associated in one complex. The 2 subunit was not associated with this complex. Taken together, these results indicate that virtually all of the nAChRs in the rat pineal gland are the 34 nAChR subtype and that the pineal gland can therefore serve as an excellent and convenient model in which to study the pharmacology and function of these receptors in a native tissue.

Address correspondence to: Dr. Kenneth J. Kellar, Department of Pharmacology, Georgetown University School of Medicine, Washington, DC 20057. E-mail: kellark{at}georgetown.edu

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