调节电压依赖性钙通道对豚鼠胆囊中胆囊收缩素和乙酰胆碱诱导收缩的影响。

Effect of modulating voltage-dependent calcium channels on cholecystokinin and acetylcholine-induced contractions of the guinea pig gallbladder.

作者信息

Parkman H P, Pagano A P, Ringold M A, Ryan J P

机构信息

Department of Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.

出版信息

Regul Pept. 1996 May 7;63(1):31-7. doi: 10.1016/0167-0115(96)00023-7.

DOI:10.1016/0167-0115(96)00023-7

PMID:8795086

Abstract

UNLABELLED

The aim of this study was to investigate the role of extracellular Ca2+ utilization in cholecystokinin (CCK) and acetylcholine-induced guinea pig gallbladder contractions by using agents that modulate influx of extracellular Ca2+ through voltage-dependent calcium channels.

METHODS

Guinea pig gallbladder muscle strips were studied isometrically at Lmax in vitro.

RESULTS

(1) Acetylcholine and CCK caused dose-dependent contractions, with EDmax of 10(-4) and 10(-6) M, respectively. (2) Preventing influx of extracellular Ca2+ by incubation in Ca(2+)-free/0.1 mM EGTA solution inhibited the acetylcholine (10(-4) M)-induced contraction by 60 +/- 3% compared to only 46 +/- 5% (P < 0.05) for CCK (10(-6) M)-induced contraction. (3) Nifedipine (3 microM) inhibited the response to acetylcholine (10(-4) M) by 54 +/- 3%, compared to only 34 +/- 3% (P < 0.01) for CCK (10(-6) M). (4) Bay K 8644 (10(-7) M) significantly increased (P < 0.05) the contractile responses to low doses of each agonist: acetylcholine (10(-6) M) by 121 +/- 44% and CCK (10(-9) M) by 94 +/- 31%, but had no effect on the contraction to the EDmax of each agonist.

CONCLUSIONS

These studies demonstrate: (1) acetylcholine and CCK cause guinea pig gallbladder contraction by both intracellular Ca2+ release and influx of extracellular Ca2+ through voltage-dependent calcium channels; (2) the CCK-induced contraction is more dependent on intracellular Ca2+ than is acetylcholine; and (3) acetylcholine and CCK-induced contractions can by modulated by manipulating influx of extracellular Ca2+ through voltage-dependent calcium channels.

摘要

未标记

本研究的目的是通过使用调节细胞外Ca2+通过电压依赖性钙通道内流的药物，研究细胞外Ca2+利用在胆囊收缩素（CCK）和乙酰胆碱诱导的豚鼠胆囊收缩中的作用。

方法

在体外等长条件下，于最大张力（Lmax）对豚鼠胆囊肌条进行研究。

结果

（1）乙酰胆碱和CCK引起剂量依赖性收缩，最大效应剂量（EDmax）分别为10(-4) M和10(-6) M。（2）在无钙/0.1 mM乙二醇双四乙酸（EGTA）溶液中孵育以阻止细胞外Ca2+内流，与CCK（10(-6) M）诱导的收缩仅被抑制46±5%相比，乙酰胆碱（10(-4) M）诱导的收缩被抑制60±3%（P<0.05）。（3）硝苯地平（3 microM）抑制对乙酰胆碱（10(-4) M）的反应达54±3%，而对CCK（10(-6) M）的反应仅被抑制34±3%（P<0.01）。（4）Bay K 8644（10(-7) M）显著增加（P<0.05）对低剂量每种激动剂的收缩反应：对乙酰胆碱（10(-6) M）增加121±44%，对CCK（10(-9) M）增加94±31%，但对每种激动剂最大效应剂量的收缩无影响。