Butcher F R, Goldman J A
Biochim Biophys Acta. 1975 May 5;392(1):82-94. doi: 10.1016/0304-4165(75)90168-3.
The role of cyclic AMP in stimulus-secretion coupling with investigated in rat parotid tissue slices in vitro. Isoproterenol and norepinephrine stimulated a rapid intracellular accumulation of cyclic AMP, which reached a maximum level of 20-30 times the control value by 5 to 10 min after addition of the drug. Isoproterenol was approximately ten times more potent in stimulating both alpha-amylase release and cyclic AMP accumulation than were norepinephrine and epinephrine, which had nearly equal effects on these two parameters. Salbutamol and phenylephrine were less effectivema parallel order of potency and sensitivity was observed for the stimulation of adenylate cyclase activity in a washed particulate fractionmthe results suggest that these drugs are acting on a parotid acinar cell through a beta1-adrenergic mechanismmat the lowest concentrations tested, each of the adrenergic agonists stimulated significant alpha-anylase release with no detectable stimulation of cyclic AMP accumulationmeven in the presence of theophylline, phenylephrine at several concentrations increased alpha-amylase release without a detectable increase in cyclic AMP levels. However, phenylephrine did stimulate adenylate cyclase. These data suggest that, under certain conditions, large increases in the intra-cellular concentration of cyclic AMP may not be necessary for stimulation of alpha-amylase release by adrenergic agonists. Also consistent with this idea was the observation that stimulation of cyclic AMP accumulation by isoproterenol was much more sensitive to inhibition by propranolol than was the stimulation of alpha-amylase release by isoproterenol. Stimulation of alpha-amylase release by phenylephrine was only partially blocked by either alpha- or beta-adrenergic blocking agents, whereas stimulation of adenylate cyclase by phenylephrine was blocked by propranolol and not by phentolaminemphenoxybenzamine and phentolamine potentiated the effects of norepinephrine and isoproterenol on both cyclic AMP accumulation and alpha-amylase release by N-6,O-2'-dibutyryl adenosine 3',5'-monophosphate; These observations may indicate a non-specific action of phenoxybenzamine, and demonstrate the need for caution in interpreting evidence obtained using alpha-adrenergic blocking agents as tools for investigation of alpha- and beta-adrenergic antagonism.
环磷酸腺苷（cAMP）在刺激-分泌偶联中的作用已在体外大鼠腮腺组织切片中进行了研究。异丙肾上腺素和去甲肾上腺素刺激cAMP在细胞内迅速积累，在添加药物后5至10分钟，其达到的最高水平为对照值的20 - 30倍。在刺激α-淀粉酶释放和cAMP积累方面，异丙肾上腺素的效力约为去甲肾上腺素和肾上腺素的十倍，而后两者对这两个参数的影响几乎相同。沙丁胺醇和去氧肾上腺素效果较差，在洗涤后的微粒部分中，观察到刺激腺苷酸环化酶活性的效力和敏感性呈平行顺序；结果表明，这些药物通过β1-肾上腺素能机制作用于腮腺腺泡细胞。在测试的最低浓度下，每种肾上腺素能激动剂均刺激了显著的α-淀粉酶释放，但未检测到对cAMP积累的刺激，即使在茶碱存在的情况下，几种浓度的去氧肾上腺素增加了α-淀粉酶释放，而cAMP水平未检测到增加。然而，去氧肾上腺素确实刺激了腺苷酸环化酶。这些数据表明，在某些条件下，肾上腺素能激动剂刺激α-淀粉酶释放可能不需要细胞内cAMP浓度大幅增加。与这一观点一致的还有以下观察结果：异丙肾上腺素刺激cAMP积累比其刺激α-淀粉酶释放对普萘洛尔的抑制更为敏感。去氧肾上腺素刺激α-淀粉酶释放仅部分被α-或β-肾上腺素能阻断剂阻断，而去氧肾上腺素刺激腺苷酸环化酶则被普萘洛尔阻断，而非酚妥拉明；酚苄明和酚妥拉明通过N - 6,O - 2'-二丁酰腺苷3',5'-单磷酸增强了去甲肾上腺素和异丙肾上腺素对cAMP积累和α-淀粉酶释放的作用；这些观察结果可能表明酚苄明具有非特异性作用，并证明在将α-肾上腺素能阻断剂作为研究α-和β-肾上腺素能拮抗作用的工具时，在解释所获得的证据时需要谨慎。
