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Pharmacological characterization of the dopamine receptor coupled to cyclic AMP formation expressed by rat mesenteric artery vascular smooth muscle cells in culture
Author(s) -
Hall Alistair S.,
Bryson Susan E.,
Vaughan Peter F.T.,
Ball Stephen G.,
Balmforth Anthony J.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13865.x
Subject(s) - fenoldopam , sch 23390 , agonist , dopamine , medicine , endocrinology , dopamine receptor , chemistry , dopamine receptor d1 , sulpiride , ibmx , dopamine antagonist , dopaminergic , dopamine receptor d2 , dopamine agonist , receptor , biology , forskolin , haloperidol
1 Mesenteric artery vascular smooth muscle cells derived from male Wistar rats and grown in culture were prelabelled with [ 3 H]‐adenine and exposed to a range of dopamine receptor agonists and antagonists. Resultant [ 3 H]‐cyclic AMP formation was determined and concentration‐effect curves constructed, in the presence of propranolol (10 −6 m ) and the phosphodiesterase inhibitor IBMX (5× 10 −4 m ). 2 K a apparent values for D 1 /DA 1 dopamine receptor agonists SKF 38393, fenoldopam, 6,7‐ADTN, and dopamine were 0.06, 0.59, 4.06 and 5.77 × 10 −6 m respectively. Although fenoldopam and SKF 38393 were more potent than dopamine, they were partial agonists with efficacies, relative to dopamine of approximately 48% and 24% respectively. 6,7‐ADTN, in contrast, behaved as a full agonist. 3 Dopamine‐stimulated cyclic AMP formation was inhibited in a concentration‐dependent manner by the D 1 /DA 1 dopamine receptor selective antagonists, SCH 23390 and cis ‐flupenthixol ( K i values 0.53 and 36.1 × 10 −1 m respectively). In contrast, the D 2 /DA 2 dopamine receptor selective antagonists, domperidone and (−)‐sulpiride, were less potent ( K i values 2.06 and 5.82 × 10 −6 m respectively). Furthermore, the stereoisomers of SCH 23390 and cis ‐flupenthixol, SCH 23388 and trans‐flupenthixol, were at least two orders of magnitude less potent ( K i values 0.14 and 13.2 × 10 −6 m respectively) indicating the stereoselective nature of this receptor. 4 Our results indicate that rat mesenteric artery vascular smooth muscle cells in culture express a dopamine receptor coupled to cyclic AMP formation, which has the pharmacological profile, characteristic of the D 1 dopamine receptor subfamily.