BIOMAT Database Logo BIOMAT Database Logo

Chronic morphine up-regulates G alpha12 and cytoskeletal proteins in Chinese hamster ovary cells expressing the cloned mu opioid receptor. 2005

Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD 21224-2735, USA.

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 mu opioid receptors and G proteins. In the present study, we hypothesized that chronic morphine alters the expression and functional effects of G alpha12, a G protein that regulates downstream cytoskeletal proteins via its control of RhoA. Our results showed that chronic morphine treatment decreased the expression of G alpha i2 (64%) and G alpha i3 (60%), had no effect of G alpha o, and increased G alpha12 (66%) expression in Chinese hamster ovary (CHO) cells expressing the cloned human mu opioid receptors (hMOR-CHO cells) but not in cells expressing a mutant mu 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 alpha-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 G alpha12 and alpha-actinin by chronic morphine was also observed in mouse brain. Viewed collectively, these findings indicate, for the first time, that chronic morphine enhances the G alpha12-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.

UI MeSH Term Description Entries
D008297 Male Males
D008813 Mice, Inbred ICR An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER. Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009020 Morphine The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. Morphine Sulfate,Duramorph,MS Contin,Morphia,Morphine Chloride,Morphine Sulfate (2:1), Anhydrous,Morphine Sulfate (2:1), Pentahydrate,Oramorph SR,SDZ 202-250,SDZ202-250,Chloride, Morphine,Contin, MS,SDZ 202 250,SDZ 202250,SDZ202 250,SDZ202250,Sulfate, Morphine
D003598 Cytoskeletal Proteins Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. Proteins, Cytoskeletal
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015854 Up-Regulation A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Up-Regulation,Upregulation,Up-Regulation (Physiology),Up Regulation
D016244 Guanosine 5'-O-(3-Thiotriphosphate) Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes. GTP gamma S,Guanosine 5'-(gamma-S)Triphosphate,gamma-Thio-GTP,GTPgammaS,Guanosine 5'-(3-O-Thio)Triphosphate,gamma S, GTP,gamma Thio GTP

Related Publications

Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Opioid peptide receptor studies. 16. Chronic morphine alters G-protein function in cells expressing the cloned mu opioid receptor.
January 2003, Synapse (New York, N.Y.),
Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Adaptations to chronic agonist exposure of mu-opioid receptor-expressing Chinese hamster ovary cells.
March 1998, European journal of pharmacology,
Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Adenylylcyclase supersensitization in mu-opioid receptor-transfected Chinese hamster ovary cells following chronic opioid treatment.
December 1995, The Journal of biological chemistry,
Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Chronic morphine treatment up-regulates mu opioid receptor binding in cells lacking filamin A.
October 2007, Brain research,
Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Effects of chronic opioid exposure on guinea pig mu opioid receptor in Chinese hamster ovary cells: comparison with human and rat receptor.
June 2007, Biochemical pharmacology,
Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Supersensitization of the adenylyl cyclase system in Chinese hamster ovary cells co-expressing cloned opioid receptors and Gz, a PTX-insensitive G protein.
May 1999, Neuroscience letters,
Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Pseudoginsenoside-F11 attenuates morphine-induced signalling in Chinese hamster ovary-mu cells.
May 2001, Neuroreport,
Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Up-regulation of RGS4 mRNA by opioid receptor agonists in PC12 cells expressing cloned mu- or kappa-opioid receptors.
December 2001, European journal of pharmacology,
Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Activity of opioid ligands in cells expressing cloned mu opioid receptors.
January 2003, BMC pharmacology,
Heng Xu, and Xiaoying Wang, and Darin Zimmerman, and Emily S Boja, and Jiabei Wang, and Edward J Bilsky, and Richard B Rothman
Neuroblastoma Neuro2A cells stably expressing a cloned mu-opioid receptor: a specific cellular model to study acute and chronic effects of morphine.
June 1995, Brain research. Molecular brain research,
Copied contents to your clipboard!