CCKA RECEPTOR ANTAGONISM INHIBITS MECHANISMS UNDERLYING CCK-8-STIMULATED INSULIN RELEASE IN ISOLATED RAT ISLETS

被引:15
作者
KARLSSON, S [1 ]
AHREN, B [1 ]
机构
[1] UNIV LUND,DEPT SURG,S-22362 LUND,SWEDEN
关键词
CCK-8 (CHOLECYSTOKININ-8); INSULIN SECRETION; ISLETS; CCKA RECEPTOR ANTAGONISTS; L-364,718; CA2+; K+; PHOSPHOINOSITIDE HYDROLYSIS;
D O I
10.1016/0014-2999(91)90301-6
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The influence of the cholecystokinin (CCK)A receptor antagonist, L-364,718, on beta-cell activation was examined in isolated perifused prelabelled rat islets. Insulin secretion and H-3 efflux from myo-[2-H-3]inositol-prelabelled islets (reflecting phosphoinositide hydrolysis) stimulated by CCK-8 (100 nM) were both inhibited by L-364,718, partially at 1 nM and totally at 10 nM. Ca-45(2+) efflux from prelabelled islets was markedly stimulated by CCK-8. This stimulation was inhibited equally by 1 and 10 nM L-364,718. CCK-8 stimulated the Rb-86(+) efflux (reflecting K+ movements) from prelabelled islets, which probably reflects an indirect effect of CCK-8 due to opening of Ca2+-activated K+ channels. This Rb-86(+) efflux was inhibited by L-364,718 at 10 nM but not affected by L-364,718 at 1 nM. It is concluded that insulin secretion, phosphoinositide hydrolysis, Ca2+ and K+ movements stimulated by CCK-8 in isolated islets are all events mediated by CCK(A) receptors. The L-364,718-induced inhibition of phosphoinositide hydrolysis was most closely correlated to the inhibition of insulin secretion. This suggests that induction of cellular events activated through stimulation of phosphoinositide hydrolysis is a major mechanism underlying CCK-8-stimulated insulin secretion.
引用
收藏
页码:253 / 257
页数:5
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