Gi-dependent suppression of β1-adrenoceptor effects in ventricular myocytes from NE-treated guinea pigs

被引:15
作者
Ranu, HK [1 ]
Mak, JCW [1 ]
Barnes, PJ [1 ]
Harding, SE [1 ]
机构
[1] Natl Heart & Lung Inst, Imperial Coll, Sch Med, London SW3 6LY, England
来源
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY | 2000年 / 278卷 / 06期
关键词
G proteins; rat; contraction; norepinephrine; radioligand binding;
D O I
10.1152/ajpheart.2000.278.6.H1807
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
It has been suggested that there is a preferential coupling in heart muscle between the inhibitory G protein (G(i)) and the beta(2)-subtype of the beta-adrenergic receptor (beta-AR), since pertussis toxin (which inactivates G(i)) reveals latent beta(2)-ARs in rat and mouse myocytes. We have previously shown that guinea pigs treated with norepinephrine (NE) for 7 days have myocytes that are desensitized to beta-AR-agonist stimulation, and that pertussis toxin restores these responses. The purpose of the present investigation was to determine whether pertussis toxin specifically upregulated beta(2)-ARs in myocytes from NE-treated guinea pigs. The sole beta-AR subtype in control guinea pig myocytes was confirmed as beta(1)-AR by radioligand binding, single-cell autoradiography, and concentration-response curves to isoproterenol in contracting myocytes. In contrast, a minor pool of beta(2)-ARs was observed in rat myocytes by use of the same methods. NE treatment decreased the maximum isoproterenol response (relative to high Ca2+) from 0.89 +/- 0.06 to 0.58 +/- 0.08 (n = 7, P < 0.01) and the pD(2) (-log EC50) from 8.8 +/- 0.2 to 7.5 +/- 0.2 (n = 7, P, 0.01). Pertussis toxin treatment increased the isoproterenolto-Ca2+ ratio to 0.88 +/- 0.04 (n = 6, P< 0.05) and the pD(2) to 8.6 +/- 0.3 (P< 0.01). This was not mediated by increases in either number or function of beta(2)-ARs. G(i) is therefore able to modulate beta(1)-AR responses in guinea pig myocytes.
引用
收藏
页码:H1807 / H1814
页数:8
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