Second messenger modulation: a novel target of future antidepressants?
During the transduction of extracellular signals within the cell, the stimulation of specific G protein-coupled receptors (GPCRs) can modulate adenylyl or guanylyl cyclase, phospholipase C activity and ion channels, which regulate second-messengers. These, in turn, trigger several biochemical cascades, including Ca(2+) release, activation of protein kinases and gene expression. Significant changes of monoamine GPCR activity may occur in patients suffering from mood disorders and the majority of antidepressants exert part of their effects through GPCR-mediated systems. The main signal transduction pathways activated by metabotropic receptors in the brain and their possible involvement in the pathophysiology of mood disorders will be reviewed herein with a special focus on the horizons opened by this approach in terms of innovative therapeutic strategies.
Marazziti
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Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, 56100 Pisa, Italy. dmarazzi@psico.med.unipi.it
Catena Dell'Osso
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Consoli
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Baroni
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D000262:Adenylyl Cyclases / Q000378:metabolism; D000928:Antidepressive Agents / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D019964:Mood Disorders / Q000188:drug therapy; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
D000928:Antidepressive Agents; D043562:Receptors, G-Protein-Coupled; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase