Arnold I R, Mistry R, Barnett D B
Department of Clinical Pharmacology, Leicester Royal Infirmary, England.
J Cardiovasc Pharmacol. 1993 Sep;22(3):481-7. doi: 10.1097/00005344-199309000-00021.
Chronic therapy with the beta 1-selective adrenoceptor partial agonist xamoterol is not associated with the tolerance observed with other beta-adrenoceptor agonists. A possible explanation is that xamoterol therapy does not desensitise human cardiac beta-adrenoceptors in vivo. beta-Adrenoceptor density and adenylate cyclase activities were determined in right atrial appendages obtained from 40 patients randomised in a double-blind fashion to receive either xamoterol or atenolol for at least 5 weeks before coronary artery bypass surgery. There was no significant difference in total or subtype beta-adrenoceptor densities, but basal and isoproterenol stimulated adenylate cyclase activity were significantly greater in the atenolol-treated group, as was the intrinsic activity of the beta 2-adrenoceptor partial agonist procaterol, suggesting that chronic therapy with xamoterol does not downregulate human cardiac beta-adrenoceptors in vivo. Coupling of beta-adrenoceptors to adenylate cyclase, predominantly mediated by the beta 2 subtype, is enhanced, however, after therapy with atenolol relative to therapy with xamoterol.
使用β1选择性肾上腺素能受体部分激动剂扎莫特罗进行长期治疗，不会出现其他β肾上腺素能受体激动剂所导致的耐受性。一种可能的解释是，扎莫特罗治疗不会在体内使人体心脏β肾上腺素能受体脱敏。对40例患者的右心耳进行了β肾上腺素能受体密度和腺苷酸环化酶活性测定，这些患者在冠状动脉搭桥手术前被随机双盲分组，分别接受扎莫特罗或阿替洛尔治疗至少5周。总β肾上腺素能受体密度或亚型密度没有显著差异，但阿替洛尔治疗组的基础和异丙肾上腺素刺激的腺苷酸环化酶活性显著更高，β2肾上腺素能受体部分激动剂丙卡特罗的内在活性也是如此，这表明扎莫特罗长期治疗不会在体内下调人体心脏β肾上腺素能受体。然而，与扎莫特罗治疗相比，阿替洛尔治疗后，主要由β2亚型介导的β肾上腺素能受体与腺苷酸环化酶的偶联增强。
