cAMP/Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle during Low pH or Contractions
cAMP/Protein Kinase A Activates Cystic Fibrosis Transmembrane Conductance Regulator for ATP Release from Rat Skeletal Muscle during Low pH or Contractions
复制标题
cAMP/蛋白激酶 A 激活囊性纤维化跨膜电导调节器，以在低 pH 值或收缩期间从大鼠骨骼肌中释放 ATP
作者：
J. Tu;Lin Lu;Weisong. Cai;H. Ballard
我们已经表明，囊性纤维化跨膜传导调节因子（CFTR）参与ATP释放骨骼肌在低pH值。这些实验研究的信号转导机制连接pH值下降CFTR激活和ATP释放，并评估是否CFTR参与ATP释放收缩肌肉。乳酸处理升高了缓冲液灌注肌肉的间质ATP和L6肌细胞的细胞外ATP：这种ATP释放被非特异性CFTR抑制剂格列本脲或特异性CFTR抑制剂CFTRinh-172消除，表明CFTR参与，并通过抑制乳酸进入细胞，表明需要细胞内pH值降低。肌肉收缩显著升高间质ATP，但CFTRinh-172消除了这种增加。cAMP/PKA通路参与CFTR调节的肌肉ATP释放的信号转导通路：毛喉素增加CFTR磷酸化并刺激肌肉或肌细胞的ATP释放;乳酸增加细胞内cAMP、pCREB和PKA活性，而IBMX增加肌细胞的ATP释放。用KT 5720抑制PKA可消除乳酸或收缩诱导的肌肉ATP释放。用阿米洛利抑制Na +/H+交换蛋白（NHE）或用SN 6或KB-R7943抑制Na +/Ca 2+交换蛋白（NCX），可消除乳酸或收缩诱导的肌肉ATP释放，表明这些交换蛋白可能参与CFTR的激活。我们的数据表明，CFTR调节释放有助于ATP释放从收缩肌肉在体内，和cAMP和PKA参与激活CFTR在肌肉收缩或酸中毒; NHE和NCX可能参与的信号转导途径。
We have shown that cystic fibrosis transmembrane conductance regulator (CFTR) is involved in ATP release from skeletal muscle at low pH. These experiments investigate the signal transduction mechanism linking pH depression to CFTR activation and ATP release, and evaluate whether CFTR is involved in ATP release from contracting muscle. Lactic acid treatment elevated interstitial ATP of buffer-perfused muscle and extracellular ATP of L6 myocytes: this ATP release was abolished by the non-specific CFTR inhibitor, glibenclamide, or the specific CFTR inhibitor, CFTRinh-172, suggesting that CFTR was involved, and by inhibition of lactic acid entry to cells, indicating that intracellular pH depression was required. Muscle contractions significantly elevated interstitial ATP, but CFTRinh-172 abolished the increase. The cAMP/PKA pathway was involved in the signal transduction pathway for CFTR-regulated ATP release from muscle: forskolin increased CFTR phosphorylation and stimulated ATP release from muscle or myocytes; lactic acid increased intracellular cAMP, pCREB and PKA activity, whereas IBMX enhanced ATP release from myocytes. Inhibition of PKA with KT5720 abolished lactic-acid- or contraction-induced ATP release from muscle. Inhibition of either the Na+/H+-exchanger (NHE) with amiloride or the Na+/Ca2+-exchanger (NCX) with SN6 or KB-R7943 abolished lactic-acid- or contraction-induced release of ATP from muscle, suggesting that these exchange proteins may be involved in the activation of CFTR. Our data suggest that CFTR-regulated release contributes to ATP release from contracting muscle in vivo, and that cAMP and PKA are involved in the activation of CFTR during muscle contractions or acidosis; NHE and NCX may be involved in the signal transduction pathway.
登录
查看更多内容
DOI：
10.1152/ajpheart.1998.275.5.h1726
发表时间：
1998-11-01
影响因子：
4.8
作者：
Sprague, RS;Ellsworth, ML;Lonigro, AJ
通讯作者：
Lonigro, AJ
影响因子：
19.6
作者：
通讯作者：
--
人类前臂动态运动期间骨骼肌间质腺苷的估计。
DOI：
10.1161/01.hyp.35.5.1124
发表时间：
2000
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Costa,F;Heusinkveld,J;Ballog,R;Davis,S;Biaggioni,I
通讯作者：
Biaggioni,I
DOI：
10.1073/pnas.90.1.312
发表时间：
1993-01-01
影响因子：
11.1
作者：
ABRAHAM, EH;PRAT, AG;CANTIELLO, HF
通讯作者：
CANTIELLO, HF