Monopoli A, Conti A, Forlani A, Ongini E
Research Laboratories, Schering-Plough S.p.A., Milan, Italy.
Pharmacol Res. 1993 Apr;27(3):273-9. doi: 10.1006/phrs.1993.1026.
We have characterized beta-adrenoceptors in the human coronary artery and investigated the mechanism underlying vasodilating activity of dilevalol, a non-selective beta-blocking agent with beta 2 agonist properties. Specific [125I]-pindolol binding was saturable, reversible and of high affinity (Kd = 91 +/- 7 pM; Bmax = 10 +/- 3 fmol/mg protein). Competition curves of [125I]-pindolol in the presence of ICI 118,551, a selective beta 2 antagonist, or CGP 20712A, a selective beta 1 antagonist, were best explained by a two-site binding model (48 +/- 5% beta 1 and 52 +/- 4% beta 2 receptors). In isolated coronary strips, isoproterenol induced a dose-dependent vasorelaxant effect which was blocked by either ICI 118,551 (100 nM) or CGP 20712A (100 nM). Dilevalol produced about 30-40% of vasodilating activity starting at a concentration of 100 nM. The response was antagonized selectively by ICI 118,551 suggesting that dilevalol produces vasodilation through the stimulation of beta 2 receptors. These findings show that in the human coronary artery both beta 1 and beta 2 receptor subtypes are present and mediate vasodilation. This suggests that the human coronary artery could be used for the evaluation of the vasodilating component of new beta-adrenoceptor blocking agents.
我们已对人冠状动脉中的β-肾上腺素能受体进行了表征，并研究了具有β2激动剂特性的非选择性β受体阻滞剂 dilevalol 的血管舒张活性机制。特异性[125I] - 吲哚洛尔结合具有饱和性、可逆性且亲和力高（Kd = 91±7 pM；Bmax = 10±3 fmol/mg 蛋白）。在选择性β2拮抗剂 ICI 118,551 或选择性β1拮抗剂 CGP 20712A 存在的情况下，[125I] - 吲哚洛尔的竞争曲线最好用双位点结合模型来解释（48±5%的β1受体和 52±4%的β2受体）。在离体冠状动脉条中，异丙肾上腺素诱导剂量依赖性血管舒张作用，该作用可被 ICI 118,551（100 nM）或 CGP 20712A（100 nM）阻断。Dilevalol 从 100 nM 的浓度开始产生约 30 - 40%的血管舒张活性。该反应被 ICI 118,551 选择性拮抗，表明 dilevalol 通过刺激β2受体产生血管舒张作用。这些发现表明，在人冠状动脉中同时存在β1和β2受体亚型，并介导血管舒张。这表明人冠状动脉可用于评估新型β-肾上腺素能受体阻滞剂的血管舒张成分。
