BIOMAT Database Logo BIOMAT Database Logo

Opioid peptide receptor studies. 16. Chronic morphine alters G-protein function in cells expressing the cloned mu opioid receptor. 2003

Heng Xu, and Yi-Feng Lu, and Richard B Rothman
Clinical Psychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.

Chronic morphine treatment results in functional uncoupling of the mu opioid receptor and its G protein in both cell culture and animal models. In the present study, Chinese hamster ovary (CHO) cells stably expressing the cloned human mu opioid receptor (hMOR-CHO cells) were incubated with 1 microM of morphine (or no drug) for 20 h. Subsequently, we assessed DAMGO- and morphine-stimulated [(35)S]-GTP-gamma-S binding and agonist-mediated inhibition of forskolin-stimulated cAMP accumulation. Using a single concentration of [(35)S]-GTP-gamma-S (0.05 nM), chronic morphine treatment did not significantly change basal [(35)S]-GTP-gamma-S binding, shifted the morphine EC(50) from 59 nM to 146 nM, and decreased the maximal stimulation (E(max)) from 201% to 177%. Similar results were observed with DAMGO. Binding surface analysis resolved two [(35)S]-GTP-gamma-S binding sites (high-affinity and low-affinity sites). In control cells, morphine stimulated [(35)S]-GTP-gamma-S binding by increasing the B(max) of the high-affinity site. In morphine-treated cells, morphine stimulated [(35)S]-GTP-gamma-S binding by decreasing the high-affinity K(d) without changing the B(max). Morphine treatment increased the EC(50) (5-11-fold) for agonist-mediated inhibition of forskolin-stimulated cAMP accumulation. These changes were not observed in cells expressing a mutant mu opioid receptor which does not develop morphine tolerance, suggesting that the changes in [(35)S]-GTP-gamma-S binding observed in hMOR-CHO cells result from the development of morphine tolerance.

UI MeSH Term Description Entries
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
D009294 Narcotics Agents that induce NARCOSIS. Narcotics include agents that cause somnolence or induced sleep (STUPOR); natural or synthetic derivatives of OPIUM or MORPHINE or any substance that has such effects. They are potent inducers of ANALGESIA and OPIOID-RELATED DISORDERS. Analgesics, Narcotic,Narcotic Analgesics,Narcotic,Narcotic Effect,Narcotic Effects,Effect, Narcotic,Effects, Narcotic
D005576 Colforsin Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland. Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
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
D000242 Cyclic AMP An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH. Adenosine Cyclic 3',5'-Monophosphate,Adenosine Cyclic 3,5 Monophosphate,Adenosine Cyclic Monophosphate,Adenosine Cyclic-3',5'-Monophosphate,Cyclic AMP, (R)-Isomer,Cyclic AMP, Disodium Salt,Cyclic AMP, Monoammonium Salt,Cyclic AMP, Monopotassium Salt,Cyclic AMP, Monosodium Salt,Cyclic AMP, Sodium Salt,3',5'-Monophosphate, Adenosine Cyclic,AMP, Cyclic,Adenosine Cyclic 3',5' Monophosphate,Cyclic 3',5'-Monophosphate, Adenosine,Cyclic Monophosphate, Adenosine,Cyclic-3',5'-Monophosphate, Adenosine,Monophosphate, Adenosine Cyclic
D000262 Adenylyl Cyclases Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP. Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
D000701 Analgesics, Opioid Compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Opioid,Opioid Analgesic,Opioid Analgesics,Opioids,Full Opioid Agonists,Opioid Full Agonists,Opioid Mixed Agonist-Antagonists,Opioid Partial Agonists,Partial Opioid Agonists,Agonist-Antagonists, Opioid Mixed,Agonists, Full Opioid,Agonists, Opioid Full,Agonists, Opioid Partial,Agonists, Partial Opioid,Analgesic, Opioid,Full Agonists, Opioid,Mixed Agonist-Antagonists, Opioid,Opioid Agonists, Full,Opioid Agonists, Partial,Opioid Mixed Agonist Antagonists,Partial Agonists, Opioid
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
D013462 Sulfur Radioisotopes Unstable isotopes of sulfur that decay or disintegrate spontaneously emitting radiation. S 29-31, 35, 37, and 38 are radioactive sulfur isotopes. Radioisotopes, Sulfur
D016466 CHO Cells CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells. CHO Cell,Cell, CHO,Cells, CHO

Related Publications

Heng Xu, and Yi-Feng Lu, and Richard B Rothman
Opioid peptide receptor studies. 17. Attenuation of chronic morphine effects after antisense oligodeoxynucleotide knock-down of RGS9 protein in cells expressing the cloned Mu opioid receptor.
June 2004, Synapse (New York, N.Y.),
Heng Xu, and Yi-Feng Lu, and Richard B Rothman
Chronic morphine up-regulates G alpha12 and cytoskeletal proteins in Chinese hamster ovary cells expressing the cloned mu opioid receptor.
October 2005, The Journal of pharmacology and experimental therapeutics,
Heng Xu, and Yi-Feng Lu, and Richard B Rothman
Activity of opioid ligands in cells expressing cloned mu opioid receptors.
January 2003, BMC pharmacology,
Heng Xu, and Yi-Feng Lu, 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,
Heng Xu, and Yi-Feng Lu, and Richard B Rothman
Mu-opioid receptor-expressing neurons in the paraventricular thalamus modulate chronic morphine-induced wake alterations.
March 2023, Translational psychiatry,
Heng Xu, and Yi-Feng Lu, and Richard B Rothman
Chronic morphine treatment increases stimulatory beta-2 adrenoceptor signaling in A431 cells stably expressing the mu opioid receptor.
January 1997, The Journal of pharmacology and experimental therapeutics,
Heng Xu, and Yi-Feng Lu, and Richard B Rothman
The interaction of the mu-opioid receptor and G protein is altered after chronic morphine treatment in rats.
November 1993, Naunyn-Schmiedeberg's archives of pharmacology,
Heng Xu, and Yi-Feng Lu, and Richard B Rothman
Identification of a novel "almost neutral" micro-opioid receptor antagonist in CHO cells expressing the cloned human mu-opioid receptor.
April 2010, Synapse (New York, N.Y.),
Heng Xu, and Yi-Feng Lu, and Richard B Rothman
Evidence for a mu-delta opioid receptor complex in CHO cells co-expressing mu and delta opioid peptide receptors.
August 2008, Peptides,
Heng Xu, and Yi-Feng Lu, and Richard B Rothman
Prenatal exposure to morphine alters brain mu opioid receptor characteristics in rats.
September 1995, Brain research,
Copied contents to your clipboard!