Shima S, Okeyama N, Oikawa S, Akamatsu N
Department of Biochemistry, St. Marianna University School of Medicine, Kanagawa, Japan.
J Toxicol Sci. 1987 Aug;12(3):309-19. doi: 10.2131/jts.12.309.
The biochemical aspects of hepatic beta-adrenergic receptors and adenylate cyclase activity in male adult rats were examined during chronic treatment of a beta-adrenergic antagonist, propranolol. The blockade of beta-adrenergic nervous systems for 7 to 10 days produced a considerable elevation of basal, glucagon, sodium fluoride, and 5'-guanylylimidodiphosphate, Gpp (NH)p-stimulated enzyme activity with a negligible response to a beta-adrenergic agonist, isoproterenol. There was no alteration in the density or the affinity of beta-adrenergic receptors for the agonist during the treatment. Guanine nucleotides have failed to induce a transformation of the higher affinity to the lower affinity state of beta-adrenergic receptors of the hepatic membrane derived either from control or the propranolol-treated animals. The activity of stimulatory guanine nucleotide regulatory proteins (Ns) in the enzyme, assessed by ADP-ribosylation was also not altered by the antagonist. These results suggest that the mechanism of the observed sensitization of adenylate cyclase induced by chronic beta-adrenergic blockade involves facilitation of Ns interaction with the catalytic subunit of the enzyme with no change in the beta-adrenergic receptor functions.
在成年雄性大鼠接受β-肾上腺素能拮抗剂普萘洛尔的长期治疗期间，对其肝脏β-肾上腺素能受体的生化特性及腺苷酸环化酶活性进行了研究。β-肾上腺素能神经系统被阻断7至10天，导致基础、胰高血糖素、氟化钠及5'-鸟苷酰亚胺二磷酸（Gpp（NH）p）刺激的酶活性显著升高，而对β-肾上腺素能激动剂异丙肾上腺素的反应可忽略不计。治疗期间，β-肾上腺素能受体对激动剂的密度或亲和力未发生改变。鸟嘌呤核苷酸未能诱导来自对照动物或普萘洛尔处理动物的肝细胞膜β-肾上腺素能受体从高亲和力状态转变为低亲和力状态。通过ADP-核糖基化评估的该酶中刺激性鸟嘌呤核苷酸调节蛋白（Ns）的活性也未因拮抗剂而改变。这些结果表明，慢性β-肾上腺素能阻断诱导的腺苷酸环化酶敏感性增加的机制涉及促进Ns与该酶催化亚基的相互作用，而β-肾上腺素能受体功能无变化。
