单羧酸类Cl^-通道阻断剂对心室肌CFTR Cl^-通道的影响

EFFECTS OF MONOCARBOXYLIC ACID DERIVATIVES ON CARDIAC VENTRICULAR CFTR Cl - CHANNELS IN GUINEA PIG

本文采用全细胞膜片箝与细胞内灌注技术，观察了单羧酸类Ｃｌ－通道阻断剂对豚鼠心室肌囊性纤维变性膜透性调节蛋白（ＣＦＴＲ）Ｃｌ－电流的影响，细胞外９ＡＣ以可逆方式增强异丙肾上腺素（ＩＳＯ）激发的ＣＦＴＲＣｌ－的外向电流成分，５ｎｉｔｒｏ２（３ｐｈｅｎｙｌｐｒｏｐｙｌａｍｉｎｏ）ｂｅｎｚｏａｔｅ（ＮＰＰＢ）和二苯胺羧酸（ＤＰＣ）对ＩＳＯ发的ＣＦＴＲＣｌ－电流的作用呈现先增强后抑制的双相效应。细胞内ＮＰＰＢ表现为增强ＩＳＯ激发作用。结果表明，单羧酸类Ｃｌ－通道阻断剂在细胞上有不同的作用位点，该类药物作用效果的差异可能与此有关。

Using the whole cell recording technique, the effects of monocarboxylic acid derivatives on cystic fibrosis transmembrane conductance regulator (CFTR) Cl - channel were examined in guinea pig ventricular myocytes. Anthracene 9 carboxylic acid (9 AC)added to the bath solution further enhanced the outward component of isoproterenol induced currents in a reversible manner, whereas 5 nitro 2 (3 phenylpropylamino) benzoic acid (NPPB) or diphenylamine 2 carboxylic acid (DPC) induced a biphasic effect on the currents. Either NPPB or DPC first produced a transient increase in the outward component of current before ensuing inhibition. Intracellular NPPB was found to potentiate isoproterenol activated currents. It is concluded that these monocarboxylic acid derivatives have different binding sites in cardiac ventricular myocytes, which might partially account for the varied effects in blocking anion channels.