title: Role of the 5-HT7 receptor in the central nervous system: from current status to future perspectives.
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.
authors.affiliation: Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Physiology, Ghent University (UGent), Ghent, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Matthys
authors.forename: Guy
authors.initials: G
authors.lastname: Haegeman
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van Craenenbroeck
authors.forename: Peter
authors.initials: P
authors.lastname: Vanhoenacker
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000502:physiology; D002490:Central Nervous System / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology; D006801:Humans; D009422:Nervous System Diseases / Q000378:metabolism / Q000473:pathology; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D012895:Sleep, REM / Q000502:physiology
chemical_list: D011985:Receptors, Serotonin; C104425:serotonin 7 receptor