西沙必利对猫结肠平滑肌功能的影响。

Effects of cisapride on feline colonic smooth muscle function.

作者信息

Washabau R J, Sammarco J

机构信息

Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 9104-6010, USA.

出版信息

Am J Vet Res. 1996 Apr;57(4):541-6.

PMID:8712522

Abstract

OBJECTIVE

To determine the effects of cisapride on feline colonic smooth muscle function.

DESIGN

In vitro smooth muscle mechanical measurements.

ANIMALS

Intact colon was obtained from healthy 2- or 3-year-old cats.

PROCEDURE

Longitudinal smooth muscle strips from proximal and distal portions of feline colon were suspended in physiologic buffer solution (37 C. 100% O2, pH 7.4), attached to isometric force transducers, and stretched to optimal muscle length. Control responses were obtained at each muscle site with acetylcholine (10(-8) to 10(-4) M), cholecystokinin (10(-11) to 10(-7) M), substance P (10(-21) to 10(-7) M), or neurotensin (10(-11) to 10(-7) M). Muscles were then stimulated with cumulative (10(-9) to 10(-6) M) or bolus (10(-6) M) doses of cisapride in the absence or presence of tetrodotoxin (10(-5) M) and atropine (10(-6) M), nifedipine (10(-6) M), or calcium-free buffer solution.

RESULTS

Cisapride stimulated contractions of longitudinal smooth muscle from proximal and distal portions of feline colon that were similar in magnitude to contractions induced by substance P and neurotensin. Cisapride contractions were only partially inhibited by tetrodotoxin (10(-6) M) and atropine (10(-6) M), suggesting that cisapride responses are only partially dependent on enteric cholinergic nerves. Nifedipine (10(-6)M) inhibited the maximal contraction to cisapride (10(-6) M) by approximately 80%. Removal of extracellular calcium did not inhibit cisapride contractions to a greater extent than did inhibition by nifedipine, indicating that calcium influx through voltage-dependent calcium channels was predominantly responsible for the dependence of the cisapride contraction on extracellular calcium.

CONCLUSIONS

Cisapride-induced contractions of feline colonic smooth muscle are largely smooth muscle-mediated and dependent on calcium influx, and are only partially dependent on enteric cholinergic nerves.

CLINICAL RELEVANCE

Cisapride may be useful in the treatment of feline colonic motility disorders.

摘要

目的

确定西沙必利对猫结肠平滑肌功能的影响。

设计

体外平滑肌力学测量。

动物

从健康的2或3岁猫获取完整结肠。

方法

将猫结肠近端和远端的纵行平滑肌条悬于生理缓冲溶液（37℃，100%氧气，pH 7.4）中，连接到等长力传感器，并拉伸至最佳肌肉长度。在每个肌肉部位用乙酰胆碱（10⁻⁸至10⁻⁴M）、胆囊收缩素（10⁻¹¹至10⁻⁷M）、P物质（10⁻²¹至10⁻⁷M）或神经降压素（10⁻¹¹至10⁻⁷M）获得对照反应。然后在不存在或存在河豚毒素（10⁻⁵M）、阿托品（10⁻⁶M）、硝苯地平（10⁻⁶M）或无钙缓冲溶液的情况下，用累积剂量（10⁻⁹至10⁻⁶M）或单次剂量（10⁻⁶M）的西沙必利刺激肌肉。

结果

西沙必利刺激猫结肠近端和远端纵行平滑肌收缩，其幅度与P物质和神经降压素诱导的收缩相似。西沙必利收缩仅部分被河豚毒素（10⁻⁶M）和阿托品（10⁻⁶M）抑制，表明西沙必利反应仅部分依赖于肠胆碱能神经。硝苯地平（10⁻⁶M）将对西沙必利（10⁻⁶M）的最大收缩抑制约80%。去除细胞外钙对西沙必利收缩的抑制程度并不比硝苯地平抑制的程度更大，表示通过电压依赖性钙通道的钙内流主要是西沙必利收缩对细胞外钙依赖性的原因。