Yoshimura K, Nezu E, Yoneyama T, Hiramatsu Y
Department of Physiology, Hokkaido University School of Dentistry, Sapporo, Japan.
Jpn J Physiol. 1987;37(5):881-97. doi: 10.2170/jjphysiol.37.881.
It was found that phenylephrine and methoxamine had two effects (one was inhibitory and the other was augmentative) on isoproterenol-stimulated cyclic AMP in rat parotid slices. The augmentation was abolished by alpha-adrenergic antagonists or by omission of calcium in the medium. Cyclic AMP accumulation by norepinephrine (NE) was significantly decreased by omission of calcium in the medium. Calmodulin antagonists, trifluoperazine and W-7, decreased NE-induced cyclic AMP accumulation, but another calmodulin antagonist, carmidazolium, did not. Phorbol ester such as 4 beta-phorbol 12-myristate, 13-acetate and phorbol 12, 13-dibutyrate, did not augment the effect of isoproterenol. These results suggest that although the influx of calcium is required in the alpha-adrenergic agonists-induced augmentation, calmodulin and protein kinase C may not be intermediates in this process. Calcium ions (10(-7) and 10(-6) M) slightly increased the activity of adenylate cyclase, but calcium (10(-6)-10(-4) M) dose-dependently inhibited the effect of isoproterenol. Therefore, calcium ions do not participate in the augmentation by directly modulating the activity of adenylate cyclase. The inhibitory effect was not affected by alpha-adrenergic antagonists. The activation of adenylate cyclase by isoproterenol was inhibited by phenylephrine with higher inhibition being obtained in lower concentrations of isoproterenol. Phenylephrine in the presence of isobutylmethylxanthine increased the amount of cyclic AMP and this effect was inhibited by propranolol, but not by phentolamine. [3H]-CGP 12177 binding of the parotid membrane was inhibited by alpha-adrenergic antagonists. These results suggest that the inhibitory effect of phenylephrine and methoxamine may be mediated by beta-adrenergic receptor.
研究发现，去氧肾上腺素和甲氧明对异丙肾上腺素刺激大鼠腮腺切片中的环磷酸腺苷（cAMP）有两种作用（一种是抑制作用，另一种是增强作用）。α-肾上腺素能拮抗剂或培养基中钙的缺失可消除这种增强作用。培养基中钙的缺失显著降低了去甲肾上腺素（NE）诱导的cAMP积累。钙调蛋白拮抗剂三氟拉嗪和W-7可降低NE诱导的cAMP积累，但另一种钙调蛋白拮抗剂卡米达唑则无此作用。佛波酯如4β-佛波醇12-肉豆蔻酸酯、13-乙酸酯和佛波醇12,13-二丁酸酯，不会增强异丙肾上腺素的作用。这些结果表明，虽然α-肾上腺素能激动剂诱导的增强作用需要钙离子内流，但钙调蛋白和蛋白激酶C可能不是此过程的中介物。钙离子（10⁻⁷和10⁻⁶M）可轻微增加腺苷酸环化酶的活性，但钙（10⁻⁶ - 10⁻⁴M）呈剂量依赖性抑制异丙肾上腺素的作用。因此，钙离子并非通过直接调节腺苷酸环化酶的活性来参与增强作用。这种抑制作用不受α-肾上腺素能拮抗剂的影响。异丙肾上腺素对腺苷酸环化酶的激活作用被去氧肾上腺素抑制，在较低浓度的异丙肾上腺素中抑制作用更强。在异丁基甲基黄嘌呤存在的情况下，去氧肾上腺素可增加cAMP的量，这种作用被普萘洛尔抑制，但不被酚妥拉明抑制。腮腺膜的[³H]-CGP 12177结合被α-肾上腺素能拮抗剂抑制。这些结果表明，去氧肾上腺素和甲氧明的抑制作用可能是由β-肾上腺素能受体介导的。
