THE β3-ADRENOCEPTOR AGONIST CL316243 PREVENTS INDOMETHACIN-INDUCED JEJUNAL ULCERATION IN THE RAT BY REVERSING EARLY VILLOUS SHORTENING
✍ Scribed by ANTHONY, ANDREW; BAHL, ASHWANI K.; OAKLEY, IAN G.; SPRAGGS, COLIN F.; DHILLON, AMAR P.; TREVETHICK, MICHAEL A.; PIASECKI, CHRISTOPHER; POUNDER, ROY E.; WAKEFIELD, ANDREW J.
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 911 KB
- Volume
- 179
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
Jejunal villi undergo early histological shortening and vascular injury in indomethacin-induced ulcerative enteropathy in the rat. The protective effects of the /I,-adrenoceptor agonist CL316243 on this rat model and the mechanism of action were examined using histological techniques. Groups of rats received oral indomethacin (15 mglkg) and oral CL316243 (0, 0-01-10 mglkg) 0.5 h beforehand. Jejunal ulceration was assessed 48 h after indomethacin. Other groups received CL316243 either 6 h before or 3 or 6 h after indomethacin. Plasma indomethacin and jejunal prostaglandin E, levels were determined in groups of rats with and without prior CL316243. CL316243 was a potent dose-dependent inhibitor of jejunal ulceration (>98 per cent inhibition at doses 20.1 mglkg; ED,,,=0.025 mglkg) but was not protective when given 6 h after indomethacin. CL316243, I mglkg, reversed early villous shortening and vascular injury. CL316243 did not affect either indomethacin bioavailability or the inhibition of prostaglandin E,. To conclude, the /l,-adrenoceptor agonist CL316243 is a potent inhibitor of indomethacin-induced jejunal ulceration and the mechanism of protection involves reversal of both villous shortening and vascular injury, which are usefully assessed by histomorphological techniques.