Quast U, Scholtysik G, Weir S W, Cook N S
Cardiovascular Department, Preclinical Research, Sandoz Ltd., Basel, Switzerland.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Jan;337(1):98-104. doi: 10.1007/BF00169484.
The experiments were undertaken to determine whether the effects of the K+ channel opener BRL 34915 on rat isolated vascular smooth muscle and atria were sensitive to pertussis toxin (PTx). PTx treatment of rats (100 micrograms/kg, infused over 15 min) affected some baseline parameters of the isolated tissues: in the atria, heart rate was increased, contractile force was decreased and the basal efflux of 86Rb+ was increased; in portal veins, the spontaneous activity was decreased but the contractility of aortic rings was unaffected. In the isolated atria removed from saline-treated rats, carbamylcholine decreased heart rate and contractile force, shortened the action potential duration by increasing the maximum rate of repolarization and increased 86Rb+ efflux. These effects of carbamylcholine were completely abolished in the atria from PTx-treated rats, demonstrating the efficacy of the toxin. The ability of 300 microM BRL 34915 and of 55 mM KCl to increase atrial 86Rb+ permeability was, however, only slightly affected by PTx treatment. In portal veins from PTx-treated rats, the efficacy of BRL 34915 to inhibit spontaneous activity and to increase 86Rb+ efflux was the same as in control organs. Similarly, in aortic rings, the ability of BRL 34915 to inhibit contractions to low concentrations of KCl or to noradrenaline was unaffected by PTx treatment as was the 86Rb+ efflux response to BRL 34915 in this tissue. It is concluded that PTx treatment does not inhibit the effects of BRL 34915 in the tissues investigated. The results are compatible with the notion that BRL 34915 does not open K+ channels by acting through a PTx-sensitive G-protein.
进行这些实验是为了确定钾通道开放剂BRL 34915对大鼠离体血管平滑肌和心房的作用是否对百日咳毒素（PTx）敏感。用PTx处理大鼠（100微克/千克，在15分钟内输注）影响了离体组织的一些基线参数：在心房中，心率增加，收缩力降低，86Rb+的基础外流增加；在门静脉中，自发活动降低，但主动脉环的收缩性未受影响。在从生理盐水处理的大鼠中取出的离体心房中，卡巴胆碱降低了心率和收缩力，通过增加最大复极速率缩短了动作电位持续时间，并增加了86Rb+外流。卡巴胆碱的这些作用在PTx处理的大鼠的心房中完全被消除，证明了毒素的有效性。然而，300微摩尔BRL 34915和55毫摩尔氯化钾增加心房86Rb+通透性的能力仅受到PTx处理的轻微影响。在PTx处理的大鼠的门静脉中，BRL 34915抑制自发活动和增加86Rb+外流的效力与在对照器官中相同。同样，在主动脉环中，BRL 34915抑制对低浓度氯化钾或去甲肾上腺素收缩的能力不受PTx处理的影响，该组织中对BRL 34915的86Rb+外流反应也不受影响。结论是，PTx处理不抑制BRL 34915在所研究组织中的作用。这些结果与BRL 34915不是通过作用于对PTx敏感的G蛋白来开放钾通道这一观点相符。
