BIOMAT Database Logo BIOMAT Database Logo

Agonist-induced desensitization of dopamine D1 receptor-stimulated adenylyl cyclase activity is temporally and biochemically separated from D1 receptor internalization. 1995

G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Department of Pharmacology, University of Toronto, Canada.

The regulation of the dopamine D1 receptor was investigated by using c-myc epitope-tagged D1 receptors expressed in Sf9 (fall armyworm ovary) cells. Treatment of D1 receptors with 10 microM dopamine for 15 min led to a loss of the dopamine-detected high-affinity state of the receptor accompanying a 40% reduction in the ability of the receptor to mediate maximal dopamine stimulation of adenylyl cyclase activity. After 60 min of agonist exposure, 45 min after the occurrence of desensitization, 28% of the cell surface receptors were internalized into an intracellular light vesicular membrane fraction as determined by radioligand binding and supported by photoaffinity labeling, immunocytochemical staining, and immunoblot analysis. Pretreatment of cells with concanavalin A or sucrose completely blocked agonist-induced D1 receptor internalization without preventing agonist-induced desensitization, indicating a biochemical separation of these processes. Collectively, these findings indicate that the desensitization of D1 receptor-coupled adenylyl cyclase activity and D1 receptor internalization are temporarily and biochemically distinct mechanisms regulating D1 receptor function following agonist activation.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D003208 Concanavalin A A MANNOSE/GLUCOSE binding lectin isolated from the jack bean (Canavalia ensiformis). It is a potent mitogen used to stimulate cell proliferation in lymphocytes, primarily T-lymphocyte, cultures.
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
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
D000345 Affinity Labels Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids. Affinity Labeling Reagents,Labeling Reagents, Affinity,Labels, Affinity,Reagents, Affinity Labeling
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

Related Publications

G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Agonist-induced desensitization of D1-dopamine receptors linked to adenylyl cyclase activity in cultured NS20Y neuroblastoma cells.
October 1990, Molecular pharmacology,
G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Decreased striatal dopamine D1 receptor-stimulated adenylyl cyclase activity in human methamphetamine users.
May 2003, The American journal of psychiatry,
G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Dopamine D1-stimulated adenylyl cyclase activity in cerebral cortex of autopsied human brain.
August 2001, Neurochemistry international,
G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Cyclic AMP-mediated desensitization of D1 dopamine receptor-coupled adenylyl cyclase in NS20Y neuroblastoma cells.
December 1994, Molecular and cellular neurosciences,
G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Desensitization of beta3-adrenergic receptor-stimulated adenylyl cyclase activity and lipolysis in rats.
January 1998, Life sciences,
G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Distinct residues in the carboxyl tail mediate agonist-induced desensitization and internalization of the human dopamine D1 receptor.
March 2002, The Journal of biological chemistry,
G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Differential effects of agonists on adenylyl cyclase superactivation mediated by the kappa opioid receptors: adenylyl cyclase superactivation is independent of agonist-induced phosphorylation, desensitization, internalization, and down-regulation.
December 2003, The Journal of pharmacology and experimental therapeutics,
G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
mu-Opioid receptors inhibit dopamine-stimulated activity of type V adenylyl cyclase but enhance dopamine-stimulated activity of type VII adenylyl cyclase.
July 1996, Molecular pharmacology,
G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Agonist-induced desensitization of adenylyl cyclase in Y1 adrenocortical tumor cells.
January 1991, Endocrine research,
G Y Ng, and J Trogadis, and J Stevens, and M Bouvier, and B F O'Dowd, and S R George
Castration blocks chronic sulpiride-induced desensitization of striatal D1 receptor-stimulated adenylate cyclase activity in male rats.
February 1989, The Journal of pharmacology and experimental therapeutics,
Copied contents to your clipboard!