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 DA₂receptors were studied using isolated vascular rings in rabbits. It was shown that (1) l-SPD(0.1～10μmol·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(0.1～100μmol·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 DA₂receptor antagonists and weak DA₁ receptor agonist with pharmacological property of dual action. 