The pharmacology and distribution of human 5‐hydroxytryptamine_2B (5‐HT_2b) receptor gene products: comparison with 5‐HT_2a and 5‐HT_2c receptors

Abstract

Full length clones of the human 5‐HT 2B receptor were isolated from human liver, kidney and pancreas. The cloned human 5‐HT 2B receptors had a high degree of homology (∼80%) with the rat and mouse 5‐HT 2B receptors. PCR amplification was used to determine the tissue distribution of human 5‐HT 2B receptor mRNA. mRNA encoding the 5‐HT 2B receptor was expressed with greatest abundance in human liver and kidney. Lower levels of expression were detected in cerebral cortex, whole brain, pancreas and spleen. Expression was not detected in heart. Northern blot analysis confirmed the presence of 5‐HT 2B 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 raises the possibility of a splice variant of the receptor or the presence of an additional homologous receptor. The human 5‐HT 2B receptor was expressed in Cos‐7 cells and its ligand binding characteristics were compared to similarly expressed human 5‐HT 2A and 5‐HT 2C receptors. The ligand specificity of the human 5‐HT 2B receptor (5‐HT > ritanserin > SB 204741 > spiperone) was distinct from that of the human 5‐HT 2A (ritanserin > spiperone > 5‐HT > SB 204741) and 5‐HT 2C (ritanserin > 5‐HT > spiperone = SB 204741) receptors. On the basis of a higher affinity for ketanserin and a lower affinity for yohimbine the human 5‐HT 2B receptor also appeared to differ from the rat 5‐HT 2B receptor. These findings confirm the sequence of the human 5‐HT 2B receptor and they demonstrate that the receptor has a widespread tissue distribution. In addition, these data suggest that there are differences in ligand affinities between different species homologues of the receptor. Finally, the finding of two distinct bands on the Northern blots of liver and kidney raises the possibility of splice variants or subtypes of 5‐HT 2B receptors, within these tissues.