BLOCKADE BY CALMODULIN INHIBITORS OF CA-2+ CHANNELS IN SMOOTH-MUSCLE FROM RAT VAS-DEFERENS

被引:42
作者
NAKAZAWA, K [1 ]
HIGO, K [1 ]
ABE, K [1 ]
TANAKA, Y [1 ]
SAITO, H [1 ]
MATSUKI, N [1 ]
机构
[1] UNIV TOKYO,FAC PHARMACEUT SCI,DEPT CHEM PHARMACOL,TOKYO 158,JAPAN
关键词
VAS DEFERENS; SMOOTH MUSCLE; CALMODULIN INHIBITORS; CALCIUM CHANNEL; DIHYDROPYRIDINE BINDING; VOLTAGE-CLAMP;
D O I
10.1111/j.1476-5381.1993.tb13543.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Effects of three compounds which are used as calmodulin inhibitors (trifluoperazine, W-7 and calmidazolium) on Ca2+ channels were investigated in smooth muscle from rat vas deferens. 2 All three calmodulin inhibitors relaxed the smooth muscle precontracted by a high concentration of KCl (63.7mM). The order of potency for the relaxation was trifluoperazine > W-7 > calmidazolium. 3 In binding studies using a microsomal fraction of vas deferens, all these calmodulin inhibitors displaced specific [H-3]-nimodipine binding. Trifluoperazine and W-7 inhibited the binding at concentrations that relaxed the smooth muscle whereas calmidazolium inhibited at concentrations much lower than those necessary for muscle relaxation. 4 Ba2+ current flowing through voltage-gated Ca2+ channels was measured under whole-cell voltage-clamp conditions in isolated smooth muscle cells. The Ba2+ current was suppressed by the three calmodulin inhibitors in the concentration-range where inhibition of [H-3]-nimodipine binding was observed. Neither voltage-dependence nor the inactivation time course of Ba2+ current were affected by these compounds. 5 The results suggest that the calmodulin inhibitors directly block Ca2+ channels in the smooth muscle cells. The channel inhibition by trifluoperazine and W-7, but perhaps not that by calmidazolium, may be responsible for the muscle relaxation observed with these compounds.
引用
收藏
页码:137 / 141
页数:5
相关论文
共 28 条
[1]   POTENTIATION BY TREATMENT WITH RESERPINE OF ALPHA-2-ADRENOCEPTOR-MEDIATED CONTRACTIONS OF RAT TAIL ARTERY [J].
ABE, K ;
SAITO, H ;
MATSUKI, N .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1989, 171 (01) :59-67
[2]   EFFECTS OF THE CALMODULIN INHIBITOR, TRIFLUOPERAZINE, ON MEMBRANE-POTENTIALS AND SLOW ACTION-POTENTIALS OF CULTURED HEART-CELLS [J].
BKAILY, G ;
SPERELAKIS, N ;
ELDEFRAWI, M .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1984, 105 (1-2) :23-31
[3]   THE EFFECTS OF BEPRIDIL, COMPARED WITH CALCIUM-CHANNEL INHIBITORS AND CALMODULIN ANTAGONISTS ON BOTH SPONTANEOUS ACTIVITY AND CONTRACTIONS INDUCED BY POTASSIUM OR PHENYLEPHRINE IN RAT PORTAL-VEIN [J].
CAMPBELL, JK ;
WINSLOW, E ;
MARSHALL, RJ .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1986, 132 (2-3) :187-196
[4]  
Chang Y., 1973, BIOCHEM PHARMACOL, V22, P3099
[5]   CALMODULIN PLAYS A PIVOTAL ROLE IN CELLULAR-REGULATION [J].
CHEUNG, WY .
SCIENCE, 1980, 207 (4426) :19-27
[6]   PARAMECIUM CALCIUM CHANNELS ARE BLOCKED BY A FAMILY OF CALMODULIN ANTAGONISTS [J].
EHRLICH, BE ;
JACOBSON, AR ;
HINRICHSEN, R ;
SAYRE, LM ;
FORTE, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (15) :5718-5722
[7]   R-24571 - A NEW POWERFUL INHIBITOR OF RED-BLOOD-CELL CA++-TRANSPORT ATPASE AND OF CALMODULIN-REGULATED FUNCTIONS [J].
GIETZEN, K ;
WUTHRICH, A ;
BADER, H .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1981, 101 (02) :418-425
[8]   IMPROVED PATCH-CLAMP TECHNIQUES FOR HIGH-RESOLUTION CURRENT RECORDING FROM CELLS AND CELL-FREE MEMBRANE PATCHES [J].
HAMILL, OP ;
MARTY, A ;
NEHER, E ;
SAKMANN, B ;
SIGWORTH, FJ .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1981, 391 (02) :85-100
[9]  
HIDAKA H, 1981, MOL PHARMACOL, V20, P571
[10]  
HIDAKA H, 1980, MOL PHARMACOL, V17, P66