Cloning, genomic organization and functionality of 5-HT7 receptor splice variants from mouse brain

The serotonin (5-HT) 5-HT7 receptors are expressed in both the central nervous system and in peripheral tissues. Receptor distribution studies and pharmacological studies have established that 5-HT7 receptors play an important role in the control of circadian rhythms and thermoregulation. Selective 5-HT7 receptor ligands have potential therapeutic applications for the treatment of pain and migraine, schizophrenia, anxiety, cognitive disturbances and inflammation.We have cloned two novel C-terminal splice variants of the 5-HT7 receptor from mouse brain. These two new splice variants have almost identical sequences as the rat 5-HT7(b) and 5-HT7(c) splice variants and so were given the same name. Ligand binding assays ([3H]5-CT), membrane localization and functional studies in transiently transfected cells indicated that all three splice variants are well expressed on the membrane and no major differences in their respective pharmacology and their ability to activate adenylyl cyclase were observed. This is in analogy with previous reports comparing either the rat or the human variants.