RT Journal Article
SR Electronic
T1 Chronic Morphine Up-Regulates Gα12 and Cytoskeletal Proteins in Chinese Hamster Ovary Cells Expressing the Cloned μ Opioid Receptor
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 248
OP 255
DO 10.1124/jpet.105.089367
VO 315
IS 1
A1 Xu, Heng
A1 Wang, Xiaoying
A1 Zimmerman, Darin
A1 Boja, Emily S.
A1 Wang, Jiabei
A1 Bilsky, Edward J.
A1 Rothman, Richard B.
YR 2005
UL http://jpet.aspetjournals.org/content/315/1/248.abstract
AB A growing body of literature indicates that chronic morphine exposure alters the expression and function of cytoskeletal proteins in addition to the well established interactions between μ opioid receptors and G proteins. In the present study, we hypothesized that chronic morphine alters the expression and functional effects of Gα12, a G protein that regulates downstream cytoskeletal proteins via its control of RhoA. Our results showed that chronic morphine treatment decreased the expression of Gαi2 (64%) and Gαi3 (60%), had no effect of Gαo, and increased Gα12 (66%) expression in Chinese hamster ovary (CHO) cells expressing the cloned human μ opioid receptors (hMOR-CHO cells) but not in cells expressing a mutant μ opioid receptor that do not develop morphine tolerance and dependence (T394A-CHO cells). Morphine treatment had no significant effect on PAR-1 thrombin receptor-activated G protein activity, as measured by thrombin-stimulated guanosine 5′-O-(3-[35S]thio)triphosphate binding. Chronic morphine treatment significantly enhanced thrombin-stimulated RhoA activity and thrombin-stimulated expression of α-actinin, a cytoskeletal anchoring protein, in hMOR-CHO cells. Proteomic analysis of two-dimensional gel spots prepared from hMOR-CHO cells showed that morphine treatment affected the expression of a number of proteins associated with morphological changes. Up-regulation of Gα12 and α-actinin by chronic morphine was also observed in mouse brain. Viewed collectively, these findings indicate, for the first time, that chronic morphine enhances the Gα12-associated signaling system, which is involved in regulating cellular morphology and growth, supporting other findings that chronic morphine may alter cellular morphology, in addition to cellular function. The American Society for Pharmacology and Experimental Therapeutics