Role of short-chain fatty acids in colonic HCO(3) secretion.
Role of short-chain fatty acids in colonic HCO(3) secretion.
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DOI：
10.1152/ajpgi.00415.2004
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发表时间：
2005-06
期刊：
影响因子：
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通讯作者：
S. Vidyasagar;C. Barmeyer;John G. Geibel;H. Binder;V. Rajendran
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文献类型：
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作者：
S. Vidyasagar;C. Barmeyer;John G. Geibel;H. Binder;V. Rajendran
管腔异丁酸是一种代谢相对较差的短链脂肪酸（SCFA），通过Cl-非依赖性、DIDS-不敏感性、载体介导的过程诱导HCO（3）分泌，并抑制Cl-依赖性和cAMP诱导的HCO（3）分泌。负责这些过程的机制尚未得到很好的表征。采用pH统计技术和微灌注技术测定了固定在Lucite小室中的离体结肠粘膜中HCO（3）的分泌。（14）C-标记丁酸盐、（14）C-标记异丁酸盐和（36）Cl摄取也通过从表面和/或隐窝细胞分离的顶膜囊泡（AMV）测定。丁酸盐对Cl-非依赖性、DIDS-不敏感的5-硝基-3-（3-苯丙氨基）苯甲酸-不敏感的HCO（3）分泌的刺激作用大于异丁酸盐，表明SCFA转运和代谢对HCO（3）分泌至关重要。管腔和丝氨酸蛋白酶25 mM丁酸盐抑制cAMP诱导的HCO（3）分泌的程度相当（98 vs. 90%）。相比之下，氯依赖性HCO（3）分泌的下调管腔25 mM丁酸盐大大超过丁酸丝氨酸（98 vs. 37%）。丁酸不能诱导离体微灌注隐窝中HCO（3）的分泌，而向外定向的HCO（3）梯度驱动可诱导表面细胞而非隐窝细胞AMV摄取（14）C-丁酸。20 mM丁酸盐可抑制AMV中的（36）Cl/HCO（3）交换和电位依赖性（36）Cl运动96-98%。我们的结论是：1）SCFA依赖性HCO（3）分泌是SCFA通过SCFA/HCO（3）交换穿过顶膜的结果，而不是细胞内SCFA代谢的结果; 2）SCFA依赖性HCO（3）分泌很可能是表面上皮细胞顶膜SCFA/HCO（3）交换的结果; 3）SCFA下调Cl-依赖性和cAMP诱导的HCO（3）分泌，分别继发于SCFA抑制顶端膜Cl/HCO（3）交换和阴离子通道活性。
Luminal isobutyrate, a relatively poor metabolized short-chain fatty acid (SCFA), induces HCO(3) secretion via a Cl-independent, DIDS-insensitive, carrier-mediated process as well as inhibiting both Cl-dependent and cAMP-induced HCO(3) secretion. The mechanism(s) responsible for these processes have not been well characterized. HCO(3) secretion was measured in isolated colonic mucosa mounted in Lucite chambers using pH stat technique and during microperfusion of isolated colonic crypts. (14)C-labeled butyrate, (14)C-labeled isobutyrate, and (36)Cl uptake were also determined by apical membrane vesicles (AMV) isolated from surface and/or crypt cells. Butyrate stimulation of Cl-independent, DIDS-insensitive 5-nitro-3-(3-phenylpropyl-amino)benzoic acid-insensitive HCO(3) secretion is greater than that by isobutyrate, suggesting that both SCFA transport and metabolism are critical for HCO(3) secretion. Both lumen and serosal 25 mM butyrate inhibit cAMP-induced HCO(3) secretion to a comparable degree (98 vs. 90%). In contrast, Cl-dependent HCO(3) secretion is downregulated by lumen 25 mM butyrate considerably more than by serosal butyrate (98 vs. 37%). Butyrate did not induce HCO(3) secretion in isolated microperfused crypts, whereas an outward-directed HCO(3) gradient-driven induced (14)C-butyrate uptake by surface but not crypt cell AMV. Both (36)Cl/HCO(3) exchange and potential-dependent (36)Cl movement in AMV were inhibited by 96-98% by 20 mM butyrate. We conclude that 1) SCFA-dependent HCO(3) secretion is the result of SCFA transport across the apical membrane via a SCFA/HCO(3) exchange more than intracellular SCFA metabolism; 2) SCFA-dependent HCO(3) secretion is most likely a result of an apical membrane SCFA/HCO(3) exchange in surface epithelial cells; 3) SCFA downregulates Cl-dependent and cAMP-induced HCO(3) secretion secondary to SCFA inhibition of apical membrane Cl/HCO(3) exchange and anion channel activity, respectively.