Premium
Regulation of Adenylyl Cyclase, ERK1/2, and CREB by G z Following Acute and Chronic Activation of the δ‐Opioid Receptor
Author(s) -
Tso Prudence H.,
Yung Lisa Y.,
Wong Yung H.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741685.x
Subject(s) - adenylyl cyclase , adcy9 , forskolin , gs alpha subunit , creb , g protein , medicine , adcy6 , adcy10 , endocrinology , camp dependent pathway , opioid , protein kinase a , chemistry , pertussis toxin , receptor , signal transduction , microbiology and biotechnology , kinase , biology , biochemistry , transcription factor , gene
Opioid tolerance and physical dependence in mammals can berapidly induced by chronic exposure to opioid agonists. Recently, opioidreceptors have been shown to interact with the pertussis toxin(PTX)‐insensitive G z (a member of the G i subfamily),which inhibits adenylyl cyclase and stimulates mitogen‐activated proteinkinases (MAPKs). Here, we established stable human embryonic kidney 293 celllines expressing δ‐opioid receptors with or without G z toexamine the role of G z in opioid receptor‐regulated signalingsystems. Each cell line was acutely or chronically treated with[D‐Pen 2 ,D‐Pen 5 ]enkephalin (DPDPE), a δ‐selectiveagonist, in the absence or presence of PTX. Subsequently, the activities ofadenylyl cyclase, cyclic AMP (cAMP)‐dependent response element‐bindingproteins (CREBs), and MAPKs were measured by determining cAMP accumulation andphosphorylation of CREBs and the extracellular signal‐regulated proteinkinases (ERKs) 1 and 2. In cells coexpressing G z , DPDPE inhibitedforskolin‐stimulated cAMP accumulation in a PTX‐insensitive manner, butG z could not replace G i to mediate adenylyl cyclasesupersensitization upon chronic opioid treatment. DPDPE‐induced adenylylcyclase supersensitization was not associated with an increase in thephosphorylation of CREBs. Both G i and G z mediatedDPDPE‐induced activation of ERK1/2, but these responses were abolished bychronic opioid treatment. Collectively, our results show that althoughG z mediated opioid‐induced inhibition of adenylyl cyclase andactivation of ERK1/2, G z alone was insufficient to mediate opioid‐induced adenylyl cyclase supersensitization.