D1 dopamine receptors of NS20Y neuroblastoma cells are functionally similar to rat striatal D1 receptors.
Dopamine or agonists with D1 receptor potency stimulated cyclic AMP (cAMP) accumulation in whole cell preparations of NS20Y neuroblastoma cells. The accumulation of cAMP after D1 stimulation was rapid and linear for 3 min. Both dopamine and the novel D1 receptor agonist dihydrexidine stimulated cAMP accumulation two- to three-fold over baseline. The pseudo-Km for dopamine was approximately 2 microM, whereas for dihydrexidine it was approximately 30 nM. The effects of both drugs were blocked by either the D1-selective antagonist SCH23390 (Ki, 0.3 nM) or the nonselective antagonist (+)-butaclamol (Ki, 5 nM). Both (-)-butaclamol and the D2-selective antagonist (-)-sulpiride were ineffective (Ki greater than 3 microM). Forskolin (10 microM), prostaglandin E1 (1 microM), and adenosine (10 microM) also stimulated cAMP accumulation, but none were antagonized by SCH23390 (1 microM). Finally, muscarinic receptor stimulation (100 microM carbachol) inhibited both D1- and forskolin-stimulated increases in cAMP accumulation by 80%. The present results indicate that NS20Y neuroblastoma cells have D1 receptors that are coupled to adenylate cyclase, and that these receptors have a pharmacological profile similar to that of the D1 receptor(s) found in rat striatum.
Lovenberg
T W
TW
Brain and Developmental Research Center, University of North Carolina School of Medicine, Chapel Hill 27599-7250.
Roth
R H
RH
Nichols
D E
DE
Mailman
R B
RB
D001552:Benzazepines / Q000378:metabolism / Q000494:pharmacology; D002069:Butaclamol / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism*; D005475:Flupenthixol / Q000494:pharmacology; D007700:Kinetics; D009447:Neuroblastoma / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D010617:Phenanthridines / Q000378:metabolism*; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D013469:Sulpiride / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
D001552:Benzazepines; D015259:Dopamine Agents; D010617:Phenanthridines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D005576:Colforsin; C061532:dihydrexidine; D010095:Oxotremorine; D013469:Sulpiride; D002217:Carbachol; D002069:Butaclamol; D000242:Cyclic AMP; D005475:Flupenthixol; D004298:Dopamine; D014403:Tubocurarine