Baird A W, Skelly M M, O'Donoghue D P, Barrett K E, Keely S J
School of Agriculture, Food Science and Veterinary Medicine and Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
Br J Pharmacol. 2008 Oct;155(4):558-66. doi: 10.1038/bjp.2008.288. Epub 2008 Jul 7.
Kinins are acknowledged as important regulators of intestinal function during inflammation; however, their effects on human intestinal ion transport have not been reported. Here, we used muscle-stripped human colonic tissue and cultured T(84)-cell monolayers to study bradykinin (BK) actions on human intestinal ion transport.
Ion transport was measured as changes in short-circuit current (I(sc)) across colonic epithelia mounted in Ussing chambers.
In intact tissue, there was a distinct polarity to BK-elicited I(sc) responses. Whereas basolateral BK stimulated sustained responses (EC(50)=0.5+/-0.1 microM), those to apical BK were more rapid and transient (EC(50)=4.1+/-1.2 nM). In T(84) cells, responses to both apical and basolateral BK were similar to those seen upon apical addition to intact tissues. Cross-desensitization between apical and basolateral domains was not observed. BK-induced responses were largely due to Cl(-) secretion as shown by their sensitivity to bumetanide and removal of Cl(-) from the bathing solution. Studies using selective agonists and antagonists indicate responses to BK are mediated by B(2) receptors. Finally, responses to basolateral BK in intact tissues were inhibited by tetrodotoxin (1 microM), atropine (1 microM), capsaicin (100 microM) and piroxicam (10 microM). BK-stimulated prostaglandin (PG)E(2) release from colonic tissue.
BK stimulates human colonic Cl(-) secretion by activation of apical and basolateral B(2) receptors. Responses to apical BK reflect a direct action on epithelial cells, whereas those to basolateral BK are amplified by stimulation of enteric nerves and PG synthesis.
激肽被认为是炎症期间肠道功能的重要调节因子；然而，其对人体肠道离子转运的影响尚未见报道。在此，我们使用剥离肌肉的人结肠组织和培养的T(84)细胞单层来研究缓激肽（BK）对人体肠道离子转运的作用。
通过测量安装在尤斯灌流小室中的结肠上皮跨膜短路电流（I(sc)）变化来检测离子转运。
在完整组织中，BK引发的I(sc)反应具有明显的极性。基底侧BK刺激产生持续反应（EC(50)=0.5±0.1微摩尔），而顶端BK引发的反应更快且更短暂（EC(50)=4.1±1.2纳摩尔）。在T(84)细胞中，对顶端和基底侧BK的反应与顶端添加到完整组织时所见的反应相似。未观察到顶端和基底侧区域之间的交叉脱敏。BK诱导的反应主要归因于Cl(-)分泌，这可通过其对布美他尼的敏感性以及从浴液中去除Cl(-)来证明。使用选择性激动剂和拮抗剂的研究表明，对BK的反应由B(2)受体介导。最后，完整组织中对基底侧BK的反应受到河豚毒素（1微摩尔）、阿托品（1微摩尔）、辣椒素（100微摩尔）和吡罗昔康（10微摩尔）的抑制。BK刺激结肠组织释放前列腺素（PG）E(2)。
BK通过激活顶端和基底侧B(2)受体刺激人结肠Cl(-)分泌。对顶端BK的反应反映了对上皮细胞的直接作用，而对基底侧BK的反应则通过刺激肠神经和PG合成而放大。
