Ubeda A, Villar A
Departamento de Farmacologia y Farmacotecnica, Facultad de Farmacia, Universidad de Valencia, Spain.
J Pharm Pharmacol. 1989 Apr;41(4):236-41. doi: 10.1111/j.2042-7158.1989.tb06442.x.
To clarify the mechanism of the vasodilatory action of khellin on calcium, we have investigated its relaxant action on base line and on K+ and noradrenaline-induced contractile tensions in rat aorta smooth muscle and on spontaneous contractile activity of rat portal vein. Khellin relaxed both of these preparations with a similar potency, which suggests a non-specific inhibition of calcium flux, without any difference related to the specific calcium channels. We have also studied the capacity of khellin to interfere with the loading and release mechanisms of caffeine and noradrenaline-sensitive calcium stores in Ca-free medium. Khellin's Ca2+ loading reduction may be related with its capacity to inhibit calcium influx. Khellin applied during Ca2+ release also caused relaxation. We propose that this drug may enhance calcium extrusion or sequestration rather than the calcium release mechanism. These actions on calcium influx and intracellular mobilization can contribute to its vasorelaxant action.
为阐明凯林对钙的血管舒张作用机制，我们研究了其对大鼠主动脉平滑肌基线、钾离子和去甲肾上腺素诱导的收缩张力以及大鼠门静脉自发收缩活动的舒张作用。凯林对这两种制剂的舒张效力相似，这表明其对钙通量具有非特异性抑制作用，与特定钙通道无关。我们还研究了凯林在无钙培养基中干扰咖啡因和去甲肾上腺素敏感钙库的装载和释放机制的能力。凯林降低钙离子装载可能与其抑制钙内流的能力有关。在钙离子释放过程中应用凯林也会导致舒张。我们认为这种药物可能增强钙的外排或螯合，而不是钙释放机制。这些对钙内流和细胞内动员的作用可能有助于其血管舒张作用。
