Anderson G F, Kohn K I
Pharmacology. 1978;16(6):306-13. doi: 10.1159/000136786.
The effects of prostaglandin (PG) E2, PGF2alpha and indomethacin (Indo) were studied on isolated detrusor smooth muscle strips in balanced salt solution and in 80 mMK+ depolarizing solution. The addition of Indo to the smooth muscle preparation at concentrations of 0.1 to 1.0 micronM produced depression of spontaneous motility that was partially antagonized by PGE2 or by elevating the extracellular Ca2+ level. Alone, both PGE2 and Ca2+ caused a marked increase in motility, increasing both frequency and amplitude. In low Ca2+, K+ depolarized bathing medium with 0.1 mM EGTA added PGE2 or PGF2alpha augmented Ca2+ contractures both in velocity and amplitude while either PG without Ca2+ had no effect on the smooth muscle. Indo produced a noncompetitive antagonism of the Ca2+ dose response curve in 80 mM K+ depolarized preparations suggesting a direct effect on Ca2+ flux. Also Indo depressed both PG and Ca2+ contractures in terms of velocity and magnitude, suggesting that Indo may act at Ca2+ channels in addition to its action on PG synthetase. These data support the work of others who suggest that PGs may augment Ca2+ permeability, acting at the Ca2+ channel or as a carrier for Ca2+ across smooth muscle cell membranes.
在平衡盐溶液和80 mM K⁺去极化溶液中,研究了前列腺素(PG)E2、PGF2α和吲哚美辛(Indo)对离体逼尿肌平滑肌条的影响。以0.1至1.0 μM的浓度向平滑肌制剂中添加Indo会导致自发运动性降低,PGE2或提高细胞外Ca²⁺水平可部分拮抗这种降低。单独使用时,PGE2和Ca²⁺均会导致运动性显著增加,频率和幅度均增加。在添加了0.1 mM EGTA的低Ca²⁺、K⁺去极化的浴液中,添加PGE2或PGF2α会使Ca²⁺挛缩在速度和幅度上均增强,而无Ca²⁺时单独使用任何一种PG对平滑肌均无影响。Indo在80 mM K⁺去极化制剂中对Ca²⁺剂量反应曲线产生非竞争性拮抗作用,表明对Ca²⁺通量有直接影响。此外,Indo在速度和幅度方面均降低了PG和Ca²⁺挛缩,这表明Indo除了作用于PG合成酶外,可能还作用于Ca²⁺通道。这些数据支持了其他人的研究工作,他们认为PG可能会增加Ca²⁺通透性,作用于Ca²⁺通道或作为Ca²⁺穿过平滑肌细胞膜的载体。