Regulation of Ca2+ sensitization by PKC and rho proteins in ovine cerebral arteries:: effects of artery size and age

被引:59
作者
Akopov, SE
Zhang, LB
Pearce, WJ [1 ]
机构
[1] Loma Linda Univ, Sch Med, Ctr Perinatal Biol, Dept Physiol, Loma Linda, CA 92350 USA
[2] Loma Linda Univ, Sch Med, Ctr Perinatal Biol, Dept Pharmacol, Loma Linda, CA 92350 USA
[3] Loma Linda Univ, Sch Med, Ctr Perinatal Biol, Dept Biochem, Loma Linda, CA 92350 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 1998年 / 275卷 / 03期
关键词
calcium sensitivity; G proteins; rho p21; maturation; serotonin; sheep;
D O I
10.1152/ajpheart.1998.275.3.H930
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
G protein-regulated Ca2+ sensitivity of vascular contractile proteins plays an important role in cerebrovascular reactivity. The present study examines the intracellular mechanisms that govern G protein-regulated Ca2+ sensitivity in cerebral arteries of different size and age. We studied beta-escin-permeabilized segments of common carotid, basilar, and middle cerebral arteries from nonpregnant adult and near-term fetal sheep. Activation of protein kinase C (PKC) by (-)-indolactam V or a phorbol ester produced receptor-independent increases in Ca2+ sensitivity. Such increases were more marked in immature arteries and were inversely correlated with artery size in both mature and immature arteries. However, inhibitors of PKC did not significantly affect increases in Ca2+ sensitivity in responses to either serotonin (5-hydroxytryptamine, 5-HT) or guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). Alternatively, deactivation of rho p21, a small G protein associated with Rho kinase, by exotoxin C3 fully prevented increases in Ca2+ sensitivity in responses to 5-HT or GTP gamma S in both adult and fetal arteries of all types. Neither inhibitors of PKC nor exotoxin C3 altered baseline Ca2+ sensitivity. We conclude that patterns of receptor- and/or G protein-mediated modulation of Ca2+ sensitivity are dependent on an intracellular pathway that involves activation of small G proteins and Rho kinase. In contrast, PKC has little, if any, role in agonist-induced Ca2+ sensitization under the present experimental conditions.
引用
收藏
页码:H930 / H939
页数:10
相关论文
共 38 条
[1]   Physiological variations in ovine cerebrovascular calcium sensitivity [J].
Akopov, SE ;
Zhang, LB ;
Pearce, WJ .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1997, 272 (05) :H2271-H2281
[2]  
Akopov SE, 1997, P SOC EXP BIOL MED, V214, P76
[3]   Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase) [J].
Amano, M ;
Ito, M ;
Kimura, K ;
Fukata, Y ;
Chihara, K ;
Nakano, T ;
Matsuura, Y ;
Kaibuchi, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (34) :20246-20249
[4]   ALTERATIONS IN CYTOPLASMIC CALCIUM SENSITIVITY DURING PORCINE CORONARY-ARTERY CONTRACTIONS AS DETECTED BY AEQUORIN [J].
BRADLEY, AB ;
MORGAN, KG .
JOURNAL OF PHYSIOLOGY-LONDON, 1987, 385 :437-448
[5]   ENHANCED GROWTH CAPACITY OF NEONATAL PULMONARY-ARTERY SMOOTH-MUSCLE CELLS IN-VITRO - DEPENDENCE ON CELL-SIZE, TIME FROM BIRTH, INSULIN-LIKE GROWTH-FACTOR-I, AND AUTO-ACTIVATION OF PROTEIN-KINASE-C [J].
DEMPSEY, EC ;
BADESCH, DB ;
DOBYNS, EL ;
STENMARK, KR .
JOURNAL OF CELLULAR PHYSIOLOGY, 1994, 160 (03) :469-481
[6]   PROTEIN SERINE THREONINE KINASES [J].
EDELMAN, AM ;
BLUMENTHAL, DK ;
KREBS, EG .
ANNUAL REVIEW OF BIOCHEMISTRY, 1987, 56 :567-613
[7]   EFFECTS OF MATURATION ON ALPHA-ADRENERGIC RECEPTOR AFFINITY AND OCCUPANCY IN SMALL CEREBRAL-ARTERIES [J].
ELLIOTT, SR ;
PEARCE, WJ .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 267 (02) :H757-H763
[8]   Inhibition of RhoA translocation and calcium sensitization by in vivo ADP-ribosylation with the chimeric toxin DC3B [J].
Fujihara, H ;
Walker, LA ;
Gong, MC ;
Lemichez, E ;
Boquet, P ;
Somlyo, AV ;
Somlyo, AP .
MOLECULAR BIOLOGY OF THE CELL, 1997, 8 (12) :2437-2447
[9]  
FUJITA A, 1995, J PHARMACOL EXP THER, V274, P555
[10]  
Gong MC, 1997, J BIOL CHEM, V272, P10704