QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.105.012369v1 68/6/1656    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Marritt, A. M. Articles by Kellar, K. J. Search for Related Content PubMed PubMed Citation Articles by Marritt, A. M. Articles by Kellar, K. J.

Nicotinic Cholinergic Receptors in the Rat Retina: Simple and Mixed Heteromeric Subtypes

Department of Pharmacology, Georgetown University School of Medicine, Washington, DC (A.M.M., B.C.C., R.P.Y., Y.X., B.B.W., K.J.K.); and Departments of Biology and Psychiatry, University of Utah, Salt Lake City, Utah (J.M.M.)

Neuronal nicotinic acetylcholine receptors (nAChRs) were measured in the rat retina to determine the heteromeric subtypes. We detected seven nicotinic receptor subunit mRNA transcripts, 2–4, 6, and 2–4, with RNase protection assays. The density of heteromeric nAChR binding sites is 3 times higher in the retina than in the cerebral cortex. Moreover, the density of the sites in the retina measured with [³H]epibatidine ([³H]EB) is 30% higher than with ¹²⁵I-3-(2(S)-azetidinylmethoxy)pyridine (A-85380) and more than twice that measured with [³H]cytisine or [³H](-)nicotine. These data suggest that the retina expresses multiple subtypes of nAChRs, including a large fraction of receptors containing the 2 subunit and a smaller fraction containing the 4 subunit. Consistent with this, in binding competition studies, nicotinic ligands fit a model for two affinity classes of binding sites, with the higher affinity sites representing 70 to 80% of the nAChRs in the retina. To determine the specific subtypes of nAChRs in the rat retina, we used subunit-specific antibodies in immunoprecipitation assays. Immunoprecipitation of [³H]EB-labeled nAChRs with antibodies specific to the 2 and 4 subunits indicated that 80% of the receptors contained 2 subunits and 25% contained 4 receptors, consistent with the binding pharmacology results. Sequential immunoprecipitation assays indicated that the rat retina contains multiple subtypes of nAChRs. The majority of the receptors measured seemed to be simple heteromeric subtypes, composed of a single type of and a single type of subunit; but a significant fraction are mixed heteromeric subtypes, composed of two or more and/or subunits.

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

This article has been cited by other articles:

				D. C. Perry, D. Mao, A. B. Gold, J. M. McIntosh, J. C. Pezzullo, and K. J. Kellar Chronic Nicotine Differentially Regulates {alpha}6- and beta3-Containing Nicotinic Cholinergic Receptors in Rat Brain J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 306 - 315. [Abstract] [Full Text] [PDF]

				D. Mao, R. P. Yasuda, H. Fan, B. B. Wolfe, and K. J. Kellar Heterogeneity of Nicotinic Cholinergic Receptors in Rat Superior Cervical and Nodose Ganglia Mol. Pharmacol., November 1, 2006; 70(5): 1693 - 1699. [Abstract] [Full Text] [PDF]

				M. J. Marks, P. Whiteaker, and A. C. Collins Deletion of the {alpha}7, beta2, or beta4 Nicotinic Receptor Subunit Genes Identifies Highly Expressed Subtypes with Relatively Low Affinity for [3H]Epibatidine Mol. Pharmacol., September 1, 2006; 70(3): 947 - 959. [Abstract] [Full Text] [PDF]