De Luca A, Tortorella V, Conte Camerino D
Dipartimento Farmacobiologico, Facoltà di Farmacia, Università di Bari, Italy.
Naunyn Schmiedebergs Arch Pharmacol. 1992 Dec;346(6):601-6. doi: 10.1007/BF00168731.
Enantiomers of 2-(p-chlorophenoxy) propionic acid, compounds acting specifically on chloride channels of adult rat skeletal muscles, have been tested on extensor digitorum longus (EDL) muscle of developing and aged rats, in an attempt to characterize the chloride channels responsible for the low chloride conductance (GCl) found in the above physiological situations. The S-(-) enantiomer, which produces a concentration-dependent inhibition of GCl in the adult EDL, is less effective in inhibiting GCl of EDL of either 2-3 weeks or 29 months old rats, particularly at low concentrations. The R-(+) isomer, which in the adult enhances GCl at low concentrations and blocks it at concentrations higher than 10 microM, lacks inhibitory action, enhancing GCl in both developing and aged EDL. At 30-40 days of age both the enantiomers produce almost the same effects exerted in adulthood. From these data we hypothesize that the low GCl found in EDL of developing and aged rats might be due not only to a lower number of conductive channels but also to the presence of a mixed population of isoforms of chloride channels having different pharmacological properties.
2-(对氯苯氧基)丙酸的对映体是一类专门作用于成年大鼠骨骼肌氯离子通道的化合物,我们已在发育中和老龄大鼠的趾长伸肌(EDL)上对其进行了测试,旨在明确在上述生理状态下导致低氯离子电导(GCl)的氯离子通道特性。S-(-)对映体在成年EDL中可产生浓度依赖性的GCl抑制作用,但在抑制2 - 3周龄或29月龄大鼠EDL的GCl方面效果较差,尤其是在低浓度时。R-(+)异构体在成年大鼠中,低浓度时可增强GCl,浓度高于10 microM时则阻断GCl,而在发育中和老龄EDL中均无抑制作用,反而增强GCl。在30 - 40日龄时,两种对映体产生的效应与成年期几乎相同。基于这些数据我们推测,发育中和老龄大鼠EDL中发现的低GCl可能不仅归因于传导通道数量减少,还可能是由于存在具有不同药理学特性的氯离子通道亚型混合群体。