洛哌丁胺通过抑制基底外侧钾离子电导对结肠上皮细胞的抗分泌作用。
Antisecretory effect of loperamide in colon epithelial cells by inhibition of basolateral K+ conductance.
作者信息
Epple H J, Fromm M, Riecken E O, Schulzke J D
机构信息
Dept. of Gastroenterology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Germany.
出版信息
Scand J Gastroenterol. 2001 Jul;36(7):731-7. doi: 10.1080/003655201300191996.
BACKGROUND
The mechanism of the antisecretory effect of loperamide was investigated in cultured highly differentiated colon epithelial cells (HT-29/B6).
METHODS
Chloride secretion was stimulated via cAMP by forskolin (FSK, 10(-5) M), via Ca2+ by the muscarinic agonist carbachol (CCh, 10(-4) M), and via protein kinase C by the phorbol ester PMA (5 x 10(-9) M). Stimulated Cl- secretion was quantified as short circuit current (I(SC)) of HT-29/B6 monolayers mounted in Ussing-type chambers.
RESULTS
Loperamide (5 x 10(-5) M) inhibited I(SC) stimulated by FSK, CCh and PMA. The antisecretory action of loperamide was unaffected by preincubation with naloxone (10(-5) M). Furthermore, loperamide strongly inhibited basolateral 86Rb efflux. Like loperamide, the calmodulin antagonist trifluoperazine (10(-4) M) inhibited I(SC) induced by FSK, CCh or PMA. The Ca2+ channel blocker verapamil (5 x 10(-5) M), on the other hand, inhibited only PMA-stimulated I(SC),but had no effect on FSK or CCh-induced I(SC) CONCLUSIONS: Loperamide exerts a direct antisecretory action on chloride secretion of colon epithelial cells independently of the respective stimulatory signal transduction pathway. This antisecretory effect is not mediated by opiate receptors and reflects inhibition of basolateral K+ conductance.
背景
在培养的高分化结肠上皮细胞（HT - 29/B6）中研究了洛哌丁胺的抗分泌作用机制。
方法
通过福斯高林（FSK，10⁻⁵ M）经环磷酸腺苷（cAMP）刺激氯离子分泌，通过毒蕈碱激动剂卡巴胆碱（CCh，10⁻⁴ M）经钙离子刺激，以及通过佛波酯PMA（5×10⁻⁹ M）经蛋白激酶C刺激。将安装在尤斯灌流小室中的HT - 29/B6单层细胞的短路电流（I(SC)）作为刺激的氯离子分泌的量化指标。
结果
洛哌丁胺（5×10⁻⁵ M）抑制了FSK、CCh和PMA刺激的I(SC)。洛哌丁胺的抗分泌作用不受与纳洛酮（10⁻⁵ M）预孵育的影响。此外，洛哌丁胺强烈抑制基底外侧⁸⁶Rb外流。与洛哌丁胺一样，钙调蛋白拮抗剂三氟拉嗪（10⁻⁴ M）抑制FSK、CCh或PMA诱导的I(SC)。另一方面，钙通道阻滞剂维拉帕米（5×10⁻⁵ M）仅抑制PMA刺激的I(SC)，但对FSK或CCh诱导的I(SC)无影响。结论：洛哌丁胺对结肠上皮细胞的氯离子分泌具有直接的抗分泌作用，独立于各自的刺激信号转导途径。这种抗分泌作用不是由阿片受体介导的，反映了对基底外侧钾离子电导的抑制。
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