Dopamine-induced functional activation of Gαq mediated by dopamine D1-like receptor in rat cerebral cortical membranes. (2nd January 2019)

• Record Type: Journal Article
• Authors: Odagaki, Yuji; Kinoshita, Masakazu; Ota, Toshio
• Is Part Of: Journal of receptor and signal transduction research. Volume 39:Number 1(2019)
• Page Start: 9
• Page End: 17
• Publication Date: 2019-01-02
• Subjects: G protein -- dopamine -- dopamine D1-like receptor -- 5-HT2A receptor -- pergolide; Cell receptors -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.1080/10799893.2018.1562470
• Languages: English
• ISSNs: 1079-9893

Abstract

Abstract: Although multiple roles of dopamine through D1 -like (D1 and D5 ) and D2 -like (D2, D3, and D4 ) receptors are initiated primarily through stimulation or inhibition of adenylyl cyclase via Gs/olf or Gi/o, respectively, there have been many reports indicating diverse signaling mechanisms that involve alternative G protein coupling. In this study, dopamine-induced Gαq activation in rat brain membranes was investigated. Agonist-induced Gαq activation was assessed by increase in guanosine-5′- O -(3-[ 35 S]thio)triphosphate ([ 35 S]GTPγS) binding to Gαq determined by [ 35 S]GTPγS binding/immunoprecipitation assay in rat brain membranes. Dopamine-stimulated Gαq functionality was highest in cortex as compared to hippocampus or striatum. In cerebral cortical membranes, this effect was mimicked by benzazepine derivatives with agonist properties at dopamine D1 -like receptors, that is, SKF83959, SKF83822, R (+)-SKF81297, R (+)-SKF38393, and SKF82958, but not by the compounds with dopamine D2 -like receptor agonist properties except for aripiprazole. Against expectation, stimulatory effects were also induced by SKF83566, R (+)-SCH23390, and pergolide. The pharmacological profiling by using a series of antagonists indicated that dopamine-induced response was mediated through dopamine D1 -like receptor, which was distinct from the receptor involved in 5-HT-induced response (5-HT2A receptor). Conversely, the responses induced by SKF83566, R (+)-SCH23390, and pergolide were most likely mediated by 5-HT2A receptor, but not by dopamine D1 -like receptor. Caution should be paid when interpreting the experimental data, especially in behavioral pharmacological research, in which SKF83566 or R (+)-SCH23390 is used as a standard selective dopamine D1 -like receptor antagonist. Also, possible clinical implications of the agonistic effects of pergolide on 5-HT2A receptor has been mentioned.