5-HT2A receptor agonists cause activation of GAq/11 proteins which in turn activate the second messenger enzyme PLC

5-HT2A receptor agonists cause activation of Gαq/11 proteins which in turn activate the second messenger enzyme PLC. Chronic treatment with olanzapine causes desensitization of this pathway as measured by either production of inositol phosphate in cells or PLC activity in brain tissue. We hypothesize that 5-HT2A receptor antagonism (induced by olanzapine) activates the Jak2/Stat3 pathway causing phosphorylated Stat3 to dimerize and translocate to the nucleus, stimulate immediate early genes and subsequently increase RGS7 transcription and RGS7 protein levels in the membrane. The increased membrane-associated RGS7 protein can then increase hydrolysis of activated Gαq/11 and result in desensitization of 5-HT2A receptor signaling.

Publication

Chronic Olanzapine Activates the Stat3 Signal Transduction Pathway and Alters Expression of Components of the 5-HT2A Receptor Signaling System in Rat Frontal Cortex. () NA Muma, et al. Neuropharmacology. ;53(4):552-562. Figure: F1. Homo sapiens

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