THE PHARMACOLOGY AND DISTRIBUTION OF HUMAN 5-HYDROXYTRYPTAMINE(2B) (5-HT2B) RECEPTOR GENE-PRODUCTS - COMPARISON WITH 5-HT2A AND 5-HT2C RECEPTORS

1 Full length clones of the human 5-HT2B receptor were isolated from h uman liver, kidney and pancreas. The cloned human 5-HT2B receptors had a high degree of homology (similar to 80%) with the rat and mouse 5-H T2B receptors. 2 PCR amplification was used to determine the tissue di stribution of human 5-HT2B receptor mRNA, mRNA encoding the 5-HT2B rec eptor was expressed with greatest abundance in human liver and kidney, Lower levels of expression were detected in cerebral cortex, whale br ain, pancreas and spleen. Expression was not detected in heart. 3 Nort hern blot analysis confirmed the presence of 5-HT2B receptor mRNA (a 2 .4 kB sized band) in pancreas, liver and kidney. An additional 3.2 kB sized band of hybridization was detected in liver and kidney. This rai ses the possibility of a splice variant of the receptor or the presenc e of an additional homologous receptor. 4 The human 5-HT2B receptor wa s expressed in Cos-7 cells and its ligand binding characteristics were compared to similarly expressed human 5-HT2A, and 5-HT2C receptors. T he ligand specificity of the human 5-HT2B receptor (5-HT > ritanserin > SB 204741 > spiperone) was distinct from that of the human 5-HT2A (r itanserin > spiperone > 5-HT > SB 204741) and 5-HT2C (ritanserin > 5-H T > spiperone = SB 204741) receptors. On the basis of a higher affinit y for ketanserin and a lower affinity for yohimbine the human 5-HT2B r eceptor also appeared to differ from the rat 5-HT2B receptor. 5 These findings confirm the sequence of the human 5-HT2B receptor and they de monstrate that the receptor has a widespread tissue distribution. In a ddition, these data suggest that there are differences in ligand affin ities between different species homologues of the receptor. Finally, t he finding of two distinct bands on the Northern blots of liver and ki dney raises the possibility of splice variants or subtypes of 5-HT2B r eceptors, within these tissues.