THE EFFECT OF CA2+ ON THE TRANSLOCATION OF PROTEIN-KINASE-C IN BOVINE TRACHEAL SMOOTH-MUSCLE

被引:3
作者
LANGLANDS, JM [1 ]
DIAMOND, J [1 ]
机构
[1] UNIV BRITISH COLUMBIA,FAC PHARMACEUT SCI,DIV PHARMACOL & TOXICOL,VANCOUVER V6T 1Z3,BC,CANADA
来源
EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION | 1994年 / 266卷 / 03期
关键词
PROTEIN KINASE C; SMOOTH MUSCLE; BOVINE; TRACHEAL; CONTRACTION; CA2+; INTRACELLULAR; BRONCHODILATOR;
D O I
10.1016/0922-4106(94)90131-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The role of calcium in protein kinase C redistribution was studied in bovine tracheal smooth muscle preparations contracted by methacholine. Previous results have shown that, in the presence of normal extracellular Ca2+, 10 mu M methacholine produced a sustained contraction and a sustained translocation of protein kinase C from the cytosol to the membrane. In the present study, when tissues were preincubated in Ca2+-free buffer containing 1 mM EGTA, methacholine produced a rapid but transient elevation in membrane-associated protein kinase C activity which was detected at 30 s and had returned to basal within 20 min. The redistribution of protein kinase C from the cytosol to the membrane induced by 1 mu M methacholine in normal Ca2+ was reversed by removal of the extracellular Ca2+ and addition of 2 mM EGTA during agonist stimulation. Removal of the Ca2+ caused approximately 50% relaxation after 10 min. Verapamil (30 mu M) partially reversed the methacholine-induced protein kinase C redistribution and caused approximately 40% relaxation after 15 min. Sodium nitroprusside (10 mu M) caused a rapid relaxation and complete reversal of the protein kinase C redistribution induced by methacholine. High K+ (60 mM) also induced a sustained contraction and redistribution of protein kinase C from the cytosol to the membrane. Suitable antagonists were added to the bathing medium to block the effects of endogenous mediators which could be released by KCl-induced depolarization. Thus, translocation of protein kinase C is obtained in the absence of receptor activation. These observations indicate that alterations in [Ca2+](i) may be responsible for the changes in protein kinase C redistribution observed during agonist-induced contractions of bovine tracheal smooth muscle.
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页码:229 / 236
页数:8
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