ENDOTHELIN - A POTENT STIMULATOR OF INTESTINAL ION SECRETION INVITRO

被引:23
作者
BROWN, MA [1 ]
SMITH, PL [1 ]
机构
[1] SMITHKLINE BEECHAM,DEPT DRUG DELIVERY,L-111,POB 1539,KING OF PRUSSIA,PA 19406
关键词
ENDOTHELIN; SECRETION; INTESTINE; PROSTAGLANDIN; LEUKOTRIENE; ION TRANSPORT;
D O I
10.1016/0167-0115(91)90191-I
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Effects of endothelin (ET) on electrical properties and Na+ and Cl- fluxes in stripped rabbit ileal mucosa were investigated in vitro in Ussing chambers. Results demonstrate that serosal addition of ET-1, ET-2, ET-3 or the precursor 38 amino acid 'big endothelin' produce dose-dependent increases in short-circuit current (I(sc)) with maximal effects at approx. 100 nM, 100 nM, 10 nM and 100 nM, respectively and half-maximal effects at 1.4 nM, 5 nM, 1.4 nM and 20 nM, respectively. Mucosal addition of ET-3 failed to elicit a response. Changes in I(sc) elicited by ET-3 are accompanied by decreases in net fluxes of both Na+ and Cl-. The cyclooxygenase inhibitors, indomethacin and piroxicam, inhibited the increase in I(sc) produced by ET-3 and indomethacin also abolished the changes in Na+ and Cl- fluxes produced by ET-3. However, no changes in the release of PGE2, thromboxane B2 or 6-keto-prostaglandin F1-alpha could be detected up to 20 min after the addition of ET-3. Preincubation of tissues with neuronal agonists or antagonists, antihistamines or an LTD4/LTE4 receptor antagonist, SKF 104353, failed to alter the response to ET-3. Furthermore, removal of serosal Ca2+ also failed to inhibit the change in I(sc) produced by ET-3. These results indicate that endothelin is a potent intestinal secretagogue which does not appear to elicit its response through stimulation of PGE2, thromboxane A2 or prostacyclin.
引用
收藏
页码:1 / 19
页数:19
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