Molecular biology of serotonin receptors.
Over the last several years the use of molecular cloning technology has revealed a vast diversity among serotonin (5-HT) receptors, whereby 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.
Baez
M
M
Lilly Research Laboratories, Indianapolis, IN 46285, USA.
Kursar
J D
JD
Helton
L A
LA
Wainscott
D B
DB
Nelson
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011985:Receptors, Serotonin / Q000032:analysis / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000502:physiology; D017385:Sequence Homology; D015398:Signal Transduction
D011985:Receptors, Serotonin; D019204:GTP-Binding Proteins