MOLECULAR-BIOLOGY OF SEROTONIN RECEPTORS

Over the last several gears the use of molecular cloning technology ha s revealed a vast diversity among serotonin (5-HT) receptors,whereby w hat was previously thought to be a family of three pharmacologically d efined classes of 5-HT receptors is actually composed of seven distinc t subfamilies designated 5-HT1-7. The 5-HT1, 5-HT2, and 5-HT5 subfamil ies currently consist of five, three and two subtypes respectively whi le the 5-HT3, 5-HT4, 5-HT6, and 5-HT7 ''subfamilies'' have at present one subtype each, Fourteen separate genes enco de 13 receptors which f all in the superfamily of G protein-coupled receptors and one ligand-g ated ion channel receptor, Our lab has contributed to the elucidation of this subtype diversity by cloning the cDNAs from both rat and human encoding the 5-HT2B receptor, This receptor subtype is equally homolo gous (approximately 70%) to the 5-HT2A and 5-HT2C receptors when amino acids comprising the transmembrane domains are compared and is clearl y the third member of the 5-HT2 subfamily, The 5-HT2B receptor has bee n shown to couple to phosphoinositide hydrolysis as do the other two m embers of this subfamily when expressed in AV12-664 cells, Limited pha rmacological analyses indicated that both rat and human 5-HT2B recepto rs are similar but distinguishable. With one tantalizing exception, th e mRNAs for these receptors appear to be similarly distributed within rat and human, The 5-HT,, receptor mRNA is not found in rat brain, whe reas in human brain it has been identified in multiple regions, This l ater finding suggests that the 5-HT2B receptor may be serving a unique CNS function in man that is absent in rat.