盐酸丙哌维林对豚鼠离体膀胱平滑肌条的钙拮抗作用  

Calcium antagonism of propiverine hydrochloride on isolated guinea pig urinary bladder

作　　者：朱焰[1] 王敏伟[2] 刘铮[2] 吴静生[2] 

机构地区：[1]上海市计划生育科学研究所中国生育调节药物毒理检测中心,上海200032 [2]沈阳药科大学药理学教研室,沈阳100015

出　　处：《中国药理学通报》2003年第7期780-783,共4页Chinese Pharmacological Bulletin

摘　　要：目的　研究盐酸丙哌维林 (P 4)对豚鼠离体膀胱平滑肌条的钙拮抗作用及作用机制。方法　采用离体平滑肌条浴槽实验方法 ,以维拉帕米为对照 ,测定P 4对CaCl2 和组胺 (His)所致离体膀胱平滑肌条的收缩及对乙酰胆碱 (ACh)所致膀胱平滑肌依赖细胞内钙、外钙收缩的影响。结果　P 41～ 1 0 0 μmol·L- 1 使CaCl2 累积量效曲线非平行右移 ,最大反应降低 ,pD2 ′为 4 73± 0 1 4。P 41 μmol·L- 1 使His量效曲线平行右移 ,最大效应不变 ,pA2 为 5 44± 0 1 4 ;1 0～ 1 0 0μmol·L- 1 使His量效曲线非平行右移 ,最大效应降低 ,pD2 ′为 4 71± 0 1 0。P 41、1 0和 1 0 0 μmol·L- 1 对ACh所致依赖细胞内钙收缩的抑制率分别为 45 77%± 6 54 %、86 2 6 %± 5 59%和 90 55 %± 3 1 1 % ,对依赖细胞外钙收缩的抑制率分别为 7 30 %± 2 89%、49 1 6 %± 6 0 9%和 88 2 5 %±3 70 %。结论　P 4低浓度时竞争性拮抗His所致膀胱平滑肌条的收缩反应 ,明显抑制膀胱平滑肌条依赖细胞内钙释放的收缩反应 ;高浓度时非竞争性拮抗His和CaCl2 所致膀胱平滑肌条的收缩反应 。AIM Calcium antagonism of propiverine hydrochloride (P 4) in isolated guinea pig urinary bladder was investigated. METHODS Bath isolated guinea pig urinary bladder in Tyrode's solution and the contraction induced by CaCl 2 , histidine (His) and acetylcholine (ACh). RESULT At doses of 1 μmol·L -1 , P 4 shifted parallelly the dose response curve for histidine (His) to the right, pA 2 is 5 44±0 14; and at doses of 10～100 μmol·L -1 , P 4 shifted the dose response curve to the right and inhibited the maximum response of His. The pD 2′ value is 4 71±0 10. P 4 shifted the dose response curve for CaCl 2 rightward and depressed the maximum response at doses of 1～100 μmol·L -1 , pD 2′ is 4 73±0 14. P 4 had a dose dependent inhibitory effect on ACh induced Ca 2+ influx in isolated guinea pig urinary bladder. The percentages of inhibition at dose of 1, 10 and 100 μmol·L -1 are 45 77%±6 54%,86 26%±5 59% and 90 55%±3 11%, respectively. P 4 inhibited contraction depending on extracellular Ca 2+ in isolated guinea pig urinary bladder, and the percentages of inhibition at dose of 1, 10 and 100 μmol·L -1 are 7 30%±2 89%, 49 16%±6 09% and 88 25%±3 70%, respectively. CONCLUSION At lower doses, P 4 showed competitive antagonism for the contraction induced by His and inhibitory effect on contraction depending on Ca 2+ influx;P 4 exhibited non competitive antagonism at higher dose for the curve or His and CaCl 2, and inhibit the contraction depending on the release of intracellular Ca 2+ and influx of extracellular Ca 2+ .

关 键 词：盐酸丙哌维林 膀胱平滑肌 维拉帕米 钙拮抗 

分 类 号：R-332[医药卫生] R322.62