CHOLECYSTOKININ-COUPLED INTRACELLULAR SIGNALING IN HUMAN GALLBLADDER MUSCLE

被引:51
作者
YU, PR
DEPETRIS, G
BIANCANI, P
AMARAL, J
BEHAR, J
机构
[1] RHODE ISL HOSP,DEPT MED,PROVIDENCE,RI 02903
[2] RHODE ISL HOSP,DEPT SURG,PROVIDENCE,RI 02902
[3] BROWN UNIV,SCH MED,PROVIDENCE,RI 02912
关键词
D O I
10.1016/0016-5085(94)90713-7
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background/Aims: It has been shown that cholecystokinin (CCK) contracts the gallbladder muscle by utilizing intracellular calcium, but the intracellular pathways have not been elucidated. The present study was designed to characterize the signal transduction pathways that mediate CCK-induced contraction of human gallbladder muscle. Methods: Single muscle cells were isolated from human gallbladders by enzymatic digestion with collagenase. Permeable cells were obtained by incubation with saponin. Protein kinase C (PKC) activity was determined by measuring the phosphorylation of a specific substrate peptide from myelin basic protein, Ac-MBP(4-14). Results: The inositol-1,4,5-tris-phosphate (IP3) antagonist heparin blocked the contractions induced by CCK. The PKC inhibitor H-7 blocked the contractions caused by low, but not high, concentrations of CCK and IP3. In contrast, the calmodulin inhibitor CGS9343B blocked the contractions induced by high, but not low, doses of CCK and IP3. Furthermore, exogenously activated calmodulin blocked the PKC-mediated contraction induced by diacylglycerol. Direct measurements of PKC activity showed that low, but not high, CCK concentrations caused PKC translocation. Conclusions: CCK contracts the gallbladder muscle via IP3-mediated calcium release. CCK activates the PKC pathway at low concentrations, whereas it activates the calmodulin pathway at high concentrations, which in turn inhibits the activation of PKC. © 1994.
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页码:763 / 770
页数:8
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