Mahé Y, Garcia-Romeu F, Motais R
Eur J Pharmacol. 1985 Oct 22;116(3):199-206. doi: 10.1016/0014-2999(85)90154-2.
In fish erythrocytes isoproterenol stimulates cellular accumulation of cyclic adenosine 3':5'-monophosphate (cyclic AMP) and produces a large increase in sodium permeability which corresponds to the activation of Na+/H+ exchanges and chloride-dependent sodium uptake. The stimulation of sodium transport by isoproterenol was reproduced by adding cyclic AMP or forskolin to the medium and was blocked by propranolol. This increase in sodium permeability was completely inhibited by amiloride at the relatively high levels (0.1-1 mM) of the diuretic required to inhibit the activity of the Na+/H+ exchanger under physiological conditions in various biological systems. It was shown that amiloride inhibited cyclic AMP accumulation. This effect, which was reversible and dose-dependent (ED50 6 X 10(-6) M-maximal effect 0.5 mM), resulted from the inhibition of the catalytic unit of adenylate cyclase. Amiloride also directly inhibited the sodium entry system but the Na transporter was less sensitive than adenylate cyclase to amiloride (ED50 6 X 10(-5) M). It appears from the data presented in this report that the inhibition of sodium permeability observed in fish erythrocytes in the presence of amiloride can result either from the effect of the diuretic on the adenylate cyclase system or from the effect on the sodium transport system, depending on the conditions in which amiloride is used. Thus, caution is required when interpreting amiloride action in terms of inhibition of specific transport processes.
在鱼类红细胞中，异丙肾上腺素刺激环磷酸腺苷（cAMP）的细胞内积累，并使钠通透性大幅增加，这与Na⁺/H⁺交换的激活以及氯离子依赖性钠摄取相对应。通过向培养基中添加cAMP或福斯可林可重现异丙肾上腺素对钠转运的刺激作用，而普萘洛尔可阻断该作用。在各种生物系统中，在生理条件下抑制Na⁺/H⁺交换器活性所需的相对高浓度（0.1 - 1 mM）的利尿剂氨氯地平，可完全抑制这种钠通透性的增加。结果表明，氨氯地平抑制cAMP积累。这种作用是可逆的且呈剂量依赖性（半数有效剂量为6×10⁻⁶ M - 最大效应为0.5 mM），是由对腺苷酸环化酶催化单位的抑制所致。氨氯地平还直接抑制钠进入系统，但钠转运体对氨氯地平的敏感性低于腺苷酸环化酶（半数有效剂量为6×10⁻⁵ M）。从本报告提供的数据来看，在氨氯地平存在的情况下，鱼类红细胞中观察到的钠通透性抑制可能是由于利尿剂对腺苷酸环化酶系统的作用，也可能是由于对钠转运系统的作用，这取决于使用氨氯地平的条件。因此，在根据抑制特定转运过程来解释氨氯地平的作用时需要谨慎。
