The 5-HT1A receptor: signaling, desensitization, and gene transcription.
The hypothesis that antianxiety or antidepressant agents (e.g., 5-HT1A agonists, 5-HT uptake blockers) exert their clinical actions via enhancement of serotonergic neurotransmission due to desensitization of 5-HT1A autoreceptors predicts that regulation of this receptor plays a crucial role in the therapeutic actions of these agents. A multidisciplinary strategy is described for the characterization of the 5-HT1A receptor at the level of cellular signaling mechanisms and genetic regulation, using heterologous expression of the cloned receptor in cell lines, site-directed mutagenesis, isolation of receptor-positive neuronal cell lines, and promoter analysis of the 5-HT1A receptor gene. These analyses will yield new insights into the possible mechanisms down-regulation of 5-HT1A receptor signaling, and may suggest novel sites of inherent defect involved in anxiety syndromes or major depression.
Albert
P R
PR
Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
Lembo
P
P
Storring
J M
JM
Charest
A
A
Saucier
C
C
D000928:Antidepressive Agents / Q000378:metabolism; D003866:Depressive Disorder / Q000378:metabolism; D006801:Humans; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D012701:Serotonin