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The cloning and expression of an OK cell cDNA encoding a 5- hydroxytryptamine1B receptor

DR Cerutis, NA Hass, LJ Iversen and DB Bylund

Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260.

Serotonin (5-hydroxytryptamine or 5-HT) is an important biogenic amine that functions as both a neurotransmitter and a hormone in the central nervous system (CNS) and the periphery. We report here the isolation of a cDNA from the OK cell that encodes a serotonin receptor (OKc1). When expressed in cultured cells, it displayed the pharmacological profile and negative coupling with adenylyl cyclase characteristic of a 5-HT1B receptor subtype. Similar to the cloned rodent 5-HT1B receptors, it had high affinity for the beta-adrenergic ligand [125I]iodocyanopindolol, because of the presence of an asparagine instead of a threonine residue in the seventh transmembrane region. The ligands used displayed the following rank order of potencies: cyanopindolol > RU24969 > methiothepin > serotonin > sumatriptan > methysergide > 8-OH-DPAT > isoproterenol. This profile correlates well (r = 0.97) with the native OK cell 5-HT1B receptor. When OKc1 is compared to the rat, mouse, and human 5-HT1B receptors, it has an amino acid sequence identity of 82%, but it is only 54% identical to the human 5-HT1D receptor.

Volume 45, Issue 1, pp. 20-28, 01/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics




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