心喘灵(XC-1)及其衍生物XC-2对肾上腺素受体及动脉平滑肌的作用

本文用放射配基结合法研究了心喘灵(XC-1)及其衍生物XC-2对肾上腺素受体的亲和力,用离体器官方法观察了二者对α受体功能的影响,用酶分析法研究了两药对β受体功能的影响。两药各种作用强度相近,对大鼠脑皮层细胞膜α受体有中等强度亲和力(Ki10^-6mol/L),对兔主动脉和大鼠肛尾肌α₁受体均有中等强度阻断作用,但对大鼠输精管突触前α₂受体只有微弱的阻断作用。二药抑制由ISO激动的腺苷酸环化酶活性的IC₅₀均为3.6×10^-5mol/L。此外,二者都能拮抗CaCl₂,KCl和5-HT引起的主动脉条收缩反应并有直接扩张血管的作用。

EFFECTS OF XINCHUANLING (XC-1) AND ITS DERIVATIVE XC-2 ON ADRENOCEPTORS AND ARTERIAL MUSCLE

Xinchuanling (XC-1) is a compound synthesized by the Henan Institute of pharmaceutical Industrial Research. (XC-2) is a derivative of XC-1. In this paper, the effects of XC-1 and XC-2 on adrenoceptors and arterial muscle were studied.XC-1 and XC-2 exhibited moderate affinity for α₁-(Ki, 2.94±0.45 and 2.71± 0.74μM) and α₂-adrenoceptor (Ki, 4.0±2.1 and 4.8+1.2μM) of rat brain cortex and a low affinity for β-adrenoceptor (Ki, 22.3 and 24.1 μM) of duck erythrocyte membrane.The intrinsic activity of XC-1 and XC-2 for α₁-adrenoceptor were determined on isolated rat anococcygeus muscle and rabbit aorta using NE as an α-adrenergic agonist. After addition of the two drugs in the medium at concentration of 10^-5, 4×10^-5 and 8×10^-5mol/L, the cumulative dose-response curve of NE was shifted to the right but the maximum response was lower than that of the control. XC-1 and XC-2 were shown to have no significant effect on presynaptic α₂-adrenoceptor in experiments using field stimulation-induced contraction of vas deferens as criterion.The adenylate cyclase (AC) of the duck erythrocyte membrane and rat lung was not activated by the two drugs. However, the effects of activation of AC by isoprenaline were inhibited by XC-1 and XC-2.The effects of the two drugs on the adrenoceptors was found to be similar.The contractions of isolated rabbit aorta induced by K²⁺ or Ca²⁺ were markedly inhibited by XC-1 and XC-2. The cumulative dose-response curves of K²⁺ and Ca²⁺ were shifted to the right by these two drugs.In addition to the effects of blocking α₁-and β-adrenoceptors and antagonism of Ca²⁺, XC-1 also diminished the 5-HT induced contractile force of rabbit aorta and exhibited a direct relaxation on this preparation. According to the multiplicity of the mode of action of these two drugs, it would appear that they may be used in the treatment of some cardiovascular diseases with little side effect.