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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

1 Mesenteric artery vascular smooth muscle cells derived from male Wistar rats and grown in culture were prelabelled with [3H]‐adenine and exposed to a range of dopamine receptor agonists and antagonists. Resultant [3H]‐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 Ka apparent values for D1/DA1 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 D1/DA1 dopamine receptor selective antagonists, SCH 23390 and cis‐flupenthixol (Ki values 0.53 and 36.1 × 10−1 m respectively). In contrast, the D2/DA2 dopamine receptor selective antagonists, domperidone and (−)‐sulpiride, were less potent (Ki 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 (Ki 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 D1 dopamine receptor subfamily.