Identification and characterization of functional D1 dopamine receptors in a human neuroblastoma cell line.
Dopamine stimulated human neuroblastoma SK-N-MC cells to accumulated cyclic AMP. The D1 agonist SKF (R)-38393 also stimulated cyclic AMP production whereas the response to dopamine was inhibited by the D1 antagonist SCH (R)-23390. Membranes from SK-N-MC cells bound the D1 ligand [125I]SCH 23982 with a Kd of 2.1 nM and a Bmax of 102 fmol/mg protein. Binding was displaced by dopamine, SKF 38393, and SCH 23390. Up to 40% of the receptors were in an agonist high affinity, guanine nucleotide-sensitive state, compared to only 6% in rat striatum. A D1 photoaffinity probe labeled a 72 kDa protein in both SK-N-MC and rat striatal membranes. Thus, SK-N-MC human neuroblastoma cells contain D1 dopamine receptors which are similar to those found in mammalian striatum, but which are more tightly coupled to adenylate cyclase. SK-N-MC cells may be a useful model to investigate the properties and regulation of D1 dopamine receptors.
Sidhu
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A
Membrane Biochemistry Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Fishman
P H
PH
D000262:Adenylyl Cyclases / Q000378:metabolism; D000345:Affinity Labels; D000818:Animals; D001552:Benzazepines / Q000031:analogs & derivatives* / Q000378:metabolism; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008970:Molecular Weight; D009447:Neuroblastoma / Q000503:physiopathology*; D051381:Rats; D011954:Receptors, Dopamine / Q000032:analysis* / Q000502:physiology; D017447:Receptors, Dopamine D1; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D000345:Affinity Labels; D001552:Benzazepines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D012701:Serotonin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D004298:Dopamine