Dagher P C, Morton T Z, Joo C S, Taglietta-Kohlbrecher A, Egnor R W, Charney A N
Nephrology Section, Department of Veterans Affairs Medical Center, New York University School of Medicine, New York 10010.
Am J Physiol. 1994 May;266(5 Pt 1):G929-34. doi: 10.1152/ajpgi.1994.266.5.G929.
We have previously demonstrated inhibition of basal Cl- secretion by intracellular bicarbonate concentration ([HCO3-]i) in rat distal colon. We now examined whether secretagogue-induced Cl- secretion is inhibited by [HCO3-]i as well. Stripped segments of distal colon from male Sprague-Dawley rats and the colon tumor cell line T84 were studied. Flux measurements were performed in the Ussing chamber under short-circuit conditions. [HCO3-]i was calculated from intracellular pH (pHi) values that were estimated with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) and carbachol were used as secretagogues. In both distal colon and T84 cells, [HCO3-]i did not affect cAMP-induced Cl- secretion. However, carbachol-induced secretion was inhibited by [HCO3-]i; in rat colon, Cl- secretion decreased from 2.3 to 1.5 mueq.cm-2.h-1 when [HCO3-]i was increased from 15.0 to 28.4 mM (P < 0.05). In T84 cells, the change in short-circuit current decreased from 8.1 to 1.1 microA/cm2 over a range of [HCO3-]i from 0 to 15.6 mM (P < 0.001). We conclude that [HCO3-]i is an important modulator of carbachol-stimulated Cl- secretion in both rat distal colon and the T84 cell line. cAMP-mediated secretion is not affected by [HCO3-]i.
我们之前已经证明，细胞内碳酸氢盐浓度（[HCO3-]i）可抑制大鼠远端结肠的基础氯离子分泌。我们现在研究促分泌剂诱导的氯离子分泌是否也受到[HCO3-]i的抑制。对雄性Sprague-Dawley大鼠的远端结肠剥离段和结肠肿瘤细胞系T84进行了研究。在短路条件下于尤斯灌流室进行通量测量。[HCO3-]i由用pH敏感染料2',7'-双（2-羧乙基）-5（6）-羧基荧光素估算的细胞内pH（pHi）值计算得出。二丁酰腺苷3',5'-环磷酸（cAMP）和卡巴胆碱用作促分泌剂。在远端结肠和T84细胞中，[HCO3-]i均不影响cAMP诱导的氯离子分泌。然而，卡巴胆碱诱导的分泌受到[HCO3-]i的抑制；在大鼠结肠中，当[HCO3-]i从15.0 mM增加到28.4 mM时，氯离子分泌从2.3微当量·厘米-2·小时-1降至1.5微当量·厘米-2·小时-1（P < 0.05）。在T84细胞中，在[HCO3-]i从0到15.6 mM的范围内，短路电流变化从8.1微安/平方厘米降至1.1微安/平方厘米（P < 0.001）。我们得出结论，[HCO3-]i是大鼠远端结肠和T84细胞系中卡巴胆碱刺激的氯离子分泌的重要调节因子。cAMP介导的分泌不受[HCO3-]i的影响。
