Cardioprotective actions of verapamil on the beta-adrenergic receptor complex in acute canine Chagas' disease.
Cardioprotective actions of verapamil on the beta-adrenergic receptor complex in acute canine Chagas' disease.
复制标题
维拉帕米对急性犬恰加斯病中β-肾上腺素能受体复合物的心脏保护作用。
DOI：
10.1006/jmcc.1996.0087
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Morris,SA
中科院分区：
文献类型：
--
作者：
Chen,G;Barr,S;Walsh,D;Rohde,S;Brewer,A;Bilezikian,JP;Wittner,M;Tanowitz,HB;Morris,SA
观察维拉帕米对急性恰加氏病犬心肌β-肾上腺素能腺苷环化酶复合体的影响。与未感染的动物相比，感染30天后。CRUZI使心肌腺酰环化酶活力降低75%以上。用维拉帕米持续治疗，感染相关的腺苷环化酶活性降低不到50%。对β-肾上腺素能受体复合体的各个组分进行了表征。感染：(1)右室(RV)β-肾上腺素能受体(β-AR)密度增加5倍，(2)左室β-AR密度降低20%，(3)左、右室高亲和力β-AR受体比例同等程度降低，(4)免疫印迹分析显示α减少50%，α_(1-3)增加，α_o无变化；(5)使依赖百日咳毒素的[~(32)P]-腺苷二磷酸核糖基化的幅度和[~(32)P]-腺苷核糖掺入α的比例降低60%。维拉帕米治疗使RVβAR受体密度、α和α_(1-3)恢复到对照水平，但对依赖百日咳毒素的[~(32)P]-腺苷核糖基化的任何方面都没有影响。治疗未感染动物的维拉帕米还：(1)增加β-肾上腺素能腺酰环化酶的活性；(2)增加右室而不是左室的βAR密度；(3)减少高到低亲和力的β-肾上腺素能受体；以及(4)仅影响αi2(减少50%)。结果表明，维拉帕米对急性恰加斯病犬β-肾上腺素能腺酰环化酶复合体的主要作用可能有助于解释其心脏保护作用。
The effect of verapamil treatment on the myocardialβ-adrenergic adenylyl cyclase complex in acute canine Chagas' disease was investigated. Relative to uninfected animals, 30 days of infection withT. cruzireduced myocardial adenylyl cyclase activity by over 75%. With continuous verapamil treatment, the infection-associated reduction in adenylyl cyclase activity was less than 50%. The individual components of theβ-adrenergic receptor complex were characterized. Infection: (1) increased right ventricular (RV)β-adrenergic receptor (βAR) density five-fold; (2) decreased left ventricleβAR density by 20%; (3) reduced the proportion of high-affinityβAR receptors to the same extent in both left and right ventricles; (4) reducedαsby 50% as determined by Western blot analysis, increasedαi1–3but did not changeαo; and (5) decreased the magnitude of pertussis-toxin-dependent [32P]ADP ribosylation by 60% as well as the proportion of [32P]ADP-ribose incorporated inαo. Verapamil treatment of infected animals restored RVβAR receptor density,αsandαi1–3to control levels but had no influence on any aspect of pertussis-toxin-dependent [32P]ADP-ribosylation. Verapamil treatment of uninfected animals also: (1) increasedβ-adrenergic adenylyl cyclase activity; (2) increasedβAR density in the RV but not the LV; (3) reduced high- to low-affinityβ-adrenergic receptors; and (4) affected onlyαi2(50% decrease). The results indicate that the major actions of verapamil on theβ-adrenergic adenylyl cyclase complex in acute canine Chagas» disease may help to account for its cardioprotective effects.