Role of the 5-HT7 receptor in the central nervous system: from current status to future perspectives

Mol Neurobiol. 2011 Jun;43(3):228-53. doi: 10.1007/s12035-011-8175-3. Epub 2011 Mar 22.

Abstract

Pharmacological and genetic tools targeting the 5-hydroxytryptamine (5-HT)7 receptor in preclinical animal models have implicated this receptor in diverse (patho)physiological processes of the central nervous system (CNS). Some data obtained with 5-HT7 receptor knockout mice, selective antagonists, and, to a lesser extent, agonists, however, are quite contradictory. In this review, we not only discuss in detail the role of the 5-HT7 receptor in the CNS but also propose some hypothetical models, which could explain the observed inconsistencies. These models are based on two novel concepts within the field of G protein-coupled receptors (GPCR), namely biphasic signaling and G protein-independent signaling, which both have been shown to be mediated by GPCR dimerization. This led us to suggest that the 5-HT7 receptor could reside in different dimeric contexts and initiate different signaling pathways, depending on the neuronal circuitry and/or brain region. In conclusion, we highlight GPCR dimerization and G protein-independent signaling as two promising future directions in 5-HT7 receptor research, which ultimately might lead to the development of more efficient dimer- and/or pathway-specific therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Body Temperature Regulation / physiology
  • Central Nervous System / metabolism*
  • Circadian Rhythm / physiology
  • Humans
  • Nervous System Diseases / metabolism
  • Nervous System Diseases / pathology
  • Receptors, Serotonin / chemistry
  • Receptors, Serotonin / metabolism*
  • Sleep, REM / physiology

Substances

  • Receptors, Serotonin
  • serotonin 7 receptor