5-HT4, 5-HT6, 5-HT7; molecular pharmacology of adenylate cyclase stimulating receptors

Abstract

Throughout the nervous system the receptors for the neurotransmitter serotonin form an unusually diverse set. Receptor-mediated responses to serotonin utilize a large collection of biochemical second messenger pathways, such as the stimulation or inhibition of adenylate cyclase activity, the hydrolysis of phosphoinositides, the mobilization of calcium and direct gating of ion channels. This diversity of structure and activity has been substantiated by the application of molecular cloning techniques which have now yielded at least 15 distinct molecular entities. The most recent subset of receptors for serotonin to be cloned are those that couple to the stimulation of adenylate cyclase activity. These subtypes: 5-HT₄, 5-HT₆ and 5-HT₇, although sharing a common signal transduction pathway, are remarkably divergent in their amino acid sequences, distribution in the brain and pharmacological properties. This digression from the expected relationships of receptor subtypes based on other serotonin receptors, as well as other biogenic amino receptor families, is unexpected and raises many questions about the extreme diversity of this signaling system.