Role of Ca2+-independent PKC in alpha(1)-adrenoceptor-mediated inotropic responses of neonatal rat hearts

被引:26
作者
Deng, XF
Mulay, S
Varma, DR
机构
[1] MCGILL UNIV, DEPT PHARMACOL & THERAPEUT, MONTREAL, PQ H3G 1Y6, CANADA
[2] MCGILL UNIV, DEPT MED, MONTREAL, PQ H3G 1Y6, CANADA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1997年 / 273卷 / 03期
关键词
protein kinase C isoforms; phosphatidylinositide; bisindolylmaleimide; diacylglycerol; phorbol 12,13-dibutyrate; thymeleatoxin; Go-6976; diacylglycerol kinase inhibitor;
D O I
10.1152/ajpheart.1997.273.3.H1113
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We investigated the role of protein kinase C (PKC) in alpha(1)-adrenoceptor (alpha(1)-AR)-mediated positive inotropic responses of neonatal rat myocardium. Bisindolylmaleimide (BIM), an inhibitor of all PKC isoforms, reduced the positive inotropic responses to phenylephrine and methoxamine but not to isoproterenol. The positive inotropic effect of phenylephrine was not attenuated by Go-6976, a selective inhibitor of Ca2+-dependent isoforms; it was potentiated by the 1,2-diacylglycerol kinase inhibitor R-59949. Phorbol 12,13-dibutyrate, an activator of both Ca2+-dependent and -independent PKC isoforms, as well as thymeleatoxin, a selective activator of Ca2+-dependent PKC isoforms, inhibited myocardial contractions, which were prevented by BIM and Go-6976. BIM inhibited the phenylephrine-induced increase in particulate PKC activity but not the increase in phosphatidylinositide turnover. Phenylephrine induced translocation of only Ca2+-independent PKC-epsilon and -delta. These results suggest that activation of Ca2+-independent PKC isoforms by alpha(1)-AR agonists plays a key role in alpha(1)-AR-mediated positive inotropic effect on neonatal myocardium.
引用
收藏
页码:H1113 / H1118
页数:6
相关论文
共 27 条
[1]   The role of diacylglycerol and activation of protein kinase C in alpha(1A)-adrenoceptor-mediated contraction to noradrenaline of rat isolated epididymal vas deferens [J].
Burt, RP ;
Chapple, CR ;
Marshall, I .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 117 (01) :224-230
[2]  
CLERK A, 1994, J BIOL CHEM, V269, P32848
[3]  
DECOURCELLES DD, 1989, J BIOL CHEM, V264, P3274
[4]   Characterization of alpha(1D)-adrenoceptor subtype in rat myocardium, aorta and other tissues [J].
Deng, XF ;
Chemtob, S ;
Varma, DR .
BRITISH JOURNAL OF PHARMACOLOGY, 1996, 119 (02) :269-276
[5]   alpha(1D)-Adrenoceptors do not contribute to inotropic responses of neonatal rat myocardium [J].
Deng, XF ;
Varma, DR .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1997, 29 (01) :57-60
[6]  
Deng XF, 1996, J PHARMACOL EXP THER, V276, P1155
[7]   PHOSPHOLIPID SIGNALING [J].
DIVECHA, N ;
IRVINE, RF .
CELL, 1995, 80 (02) :269-278
[8]   INOTROPIC EFFECTS OF STAUROSPORINE, NA-0345 AND H-7, PROTEIN-KINASE-C INHIBITORS, ON RABBIT VENTRICULAR MYOCARDIUM - SELECTIVE-INHIBITION OF THE POSITIVE INOTROPIC EFFECT MEDIATED BY ALPHA(1)-ADRENOCEPTORS [J].
ENDOH, M ;
NOROTA, I ;
TAKANASHI, M ;
KASAI, H .
JAPANESE JOURNAL OF PHARMACOLOGY, 1993, 63 (01) :17-26
[9]   PROTEIN-KINASE-C IS NOT INVOLVED IN ALPHA-1-ADRENOCEPTOR-MEDIATED POSITIVE INOTROPIC EFFECT [J].
ENDOU, M ;
HATTORI, Y ;
TOHSE, N ;
KANNO, M .
AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 260 (01) :H27-H36
[10]   alpha(1)-Adrenergic receptor subtypes - Molecular structure, function, and signaling [J].
Graham, RM ;
Perez, DM ;
Hwa, J ;
Piascik, MT .
CIRCULATION RESEARCH, 1996, 78 (05) :737-749