PT  - JOURNAL ARTICLE
AU  - Heng Xu
AU  - Xiaoying Wang
AU  - Darin Zimmerman
AU  - Emily S. Boja
AU  - Jiabei Wang
AU  - Edward J. Bilsky
AU  - Richard B. Rothman
TI  - Chronic Morphine Up-Regulates Gα12 and Cytoskeletal Proteins in Chinese Hamster Ovary Cells Expressing the Cloned μ Opioid Receptor
AID  - 10.1124/jpet.105.089367
DP  - 2005 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 248--255
VI  - 315
IP  - 1
4099  - http://jpet.aspetjournals.org/content/315/1/248.short
4100  - http://jpet.aspetjournals.org/content/315/1/248.full
SO  - J Pharmacol Exp Ther2005 Oct 01; 315
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