A68930 is a potent, full agonist at dopamine1 (D1) receptors in renal epithelial LLC-PK1 cells.
The selective dopamine1 (D1) receptor agonists SK&F 82526 (fenoldopam) and A68930 and the mixed D1/D2 agonist SK&F 85174 were tested for their ability to stimulate adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation in the porcine renal epithelial cell line, LLC-PK1. SK&F 82526 and SK&F 85174 were potent stimulators of cyclic AMP accumulation (EC50s 21.4 and 14.5 nM, respectively), but only partial agonists (intrinsic activities 31% and 46% of dopamine respectively). In contrast, A68930 was a potent, full agonist (EC50 12.7 nM, intrinsic activity 102% of dopamine). The stimulatory effects of A68930 and dopamine on cyclic AMP accumulation were not additive, and the stimulation of cyclic AMP accumulation by A68930 was blocked by the D1-selective antagonist, SCH 23390. These properties of A68930 suggest that it may be a useful D1-selective agonist to study renal D1 receptor mechanisms in vitro and in vivo.
Grenader
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Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, NY 10029.
Healy
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DP
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D018818:Fenoldopam; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000187:drug effects*
D001552:Benzazepines; D002839:Chromans; D015259:Dopamine Agents; D017447:Receptors, Dopamine D1; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C045977:SK&F 85174; C065380:A 68930; D000242:Cyclic AMP; D018818:Fenoldopam; D004298:Dopamine