[Effects of l-stepholidine on the peripheral vascular dopamine DA1 and DA2 receptor subtypes]

The effects of l-stepholidine(l-SPD) on peripheral vascular dopamine DA1 and DA2 receptors were studied using isolated vascular rings in rabbits. It was shown that (1) l-SPD(0.1-10 mumol.L-1) shifted the dose-response curves to the right in a nonparallel fashion and decreased the maximal response (Emax) of both the fenoldopam(FODA, a selective DA1 agonist)-induced and the propyl-buty-dopamine(PBDA, a selective DA2 agonist)-induced vasorelaxation showing a non-competitive antagonistic action. The pD2 values of l-SPD for FODA in the renal, pulmonary and mesenteric arteries were 5.43, 5.48 and 5.58, respectively. The pD2 values for PBDA in the mesenteric and femoral arteries were 5.35 and 5.89, respectively. The potencies of its antagonistic action were comparable to SCH23390, a selective DA1 antagonist, and to domperidone, a selective DA2 antagonist. (2) l-SPD(0.1-100 mumol.L-1) per se was also found to induce slight but dose-related vasorelaxations in the renal and pulmonary arteries displaying its DA1 agonistic activity. Its pD2 values were 4.98 and 5.02, respectively. However, its Emax were considerably smaller than that of FODA. These results suggest that l-SPD is a mixed peripheral DA1 and DA2 receptor antagonists and weak DA1 receptor agonist with pharmacological property of dual action.