Braunstein G M, Roman R M, Clancy J P, Kudlow B A, Taylor A L, Shylonsky V G, Jovov B, Peter K, Jilling T, Ismailov I I, Benos D J, Schwiebert L M, Fitz J G, Schwiebert E M
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005, USA.
J Biol Chem. 2001 Mar 2;276(9):6621-30. doi: 10.1074/jbc.M005893200. Epub 2000 Nov 10.
These studies provide evidence that cystic fibrosis transmembrane conductance regulator (CFTR) potentiates and accelerates regulatory volume decrease (RVD) following hypotonic challenge by an autocrine mechanism involving ATP release and signaling. In wild-type CFTR-expressing cells, CFTR augments constitutive ATP release and enhances ATP release stimulated by hypotonic challenge. CFTR itself does not appear to conduct ATP. Instead, ATP is released by a separate channel, whose activity is potentiated by CFTR. Blockade of ATP release by ion channel blocking drugs, gadolinium chloride (Gd(3+)) and 4,4'-diisothiocyanatostilbene-2,2'disulfonic acid (DIDS), attenuated the effects of CFTR on acceleration and potentiation of RVD. These results support a key role for extracellular ATP and autocrine and paracrine purinergic signaling in the regulation of membrane ion permeability and suggest that CFTR potentiates ATP release by stimulating a separate ATP channel to strengthen autocrine control of cell volume regulation.
这些研究提供了证据，表明囊性纤维化跨膜传导调节因子（CFTR）通过涉及ATP释放和信号传导的自分泌机制，在低渗刺激后增强并加速调节性容积减小（RVD）。在表达野生型CFTR的细胞中，CFTR增加组成性ATP释放，并增强低渗刺激所激发的ATP释放。CFTR本身似乎并不传导ATP。相反，ATP由一个单独的通道释放，该通道的活性由CFTR增强。离子通道阻断药物氯化钆（Gd(3+)）和4,4'-二异硫氰酸芪-2,2'-二磺酸（DIDS）对ATP释放的阻断，减弱了CFTR对RVD加速和增强的作用。这些结果支持细胞外ATP以及自分泌和旁分泌嘌呤能信号在膜离子通透性调节中的关键作用，并表明CFTR通过刺激一个单独的ATP通道来增强ATP释放，从而加强对细胞容积调节的自分泌控制。
