Molecular Biology of Serotonin Receptors

Publisher Website
Google Scholar
Abstract
Over the last several years the use of molecular cloning technology has revealed a vast diversity among serotonin (5‐HT)receptors, where by what was previously thought to be a family of three pharmacologically defined classes of 5‐HT receptors is actually composed of seven distinct subfamilies designated 5‐HT1–7. The 5‐HT1, 5‐HT2, and 5‐HT5 subfamilies currently consist of five, three and two subtypes respectively while the 5‐HT3,5‐HT4, 5‐HT6, and 5‐HT7 “subfamilies” have at present one subtype each. Fourteen separate genes encode 13 receptors which fall in the superfamily of G protein‐coupled receptors and one ligand‐gated 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 homologous (approximately 70%) to the 5‐HT2A and 5‐HT2C receptors when amino acids comprising the transmembrane domains are compared and is clearly the third member of the 5‐HT2 subfamily. The 5‐HT2B receptor has been shown to couple to phosphoinositide hydrolysis as do the other two members of this subfamily when expressed in AV12‐664 cells. Limited pharmacological analyses indicated that both rat and human 5‐HT2B receptors are similar but distinguishable. With one tantalizing exception, the mRNAs for these receptors appear to be similarly distributed within rat and human. The 5‐HT2B receptor mRNA is not found in rat brain, whereas in human brain it has been identified in multiple regions. This later finding suggests that the 5‐HT2B receptor may be serving a unique CNS function in man that is absent in rat.