Niewoehner D E, Campe H, Duane S, McGowan T, Montgomery M R
J Appl Physiol Respir Environ Exerc Physiol. 1979 Aug;47(2):330-6. doi: 10.1152/jappl.1979.47.2.330.
Airway smooth muscle preparations from various sites and species exhibit a range of sensitivities to the same beta-adrenergic agonist. This variability has been attributed to beta-receptor function but the exact mechanism determining the response has not been identified. After first inducing contraction with acetylcholine, we measured isoproterenol and theophylline relaxation responses in five separate airway smooth muscle preparations in vitro. The order of sensitivity was identical for both drugs: guinea pig trachea greater than dog lung strip greater than dog bronchiole greater than rat trachea greater than dog trachea. Because of evidence that both drugs act by increasing adenosine 3',5'-cyclic monophosphate (cAMP) concentrations, we utilized a kinetic model of cAMP metabolism to investigate the possibility that the identical order of sensitivity to both drugs could be explained by a common mechanism. Relaxation responses to both drugs are in accord with known kinetic data. Small differences in the velocity constants of enzymes affecting cAMP metabolism or differences in the relaxation response to the same concentrations of cAMP can fully explain the variable muscle responses to both drugs.
来自不同部位和物种的气道平滑肌制剂对同一种β-肾上腺素能激动剂表现出一系列敏感性。这种变异性归因于β受体功能，但决定反应的具体机制尚未确定。在用乙酰胆碱首先诱导收缩后，我们在体外测量了五种不同气道平滑肌制剂中异丙肾上腺素和茶碱的舒张反应。两种药物的敏感性顺序相同：豚鼠气管＞狗肺条＞狗细支气管＞大鼠气管＞狗气管。由于有证据表明两种药物均通过增加3',5'-环磷酸腺苷（cAMP）浓度起作用，我们利用cAMP代谢动力学模型来研究两种药物敏感性相同顺序是否可由共同机制解释的可能性。对两种药物的舒张反应与已知动力学数据一致。影响cAMP代谢的酶的速度常数的微小差异或对相同浓度cAMP的舒张反应差异可充分解释肌肉对两种药物的可变反应。
