Suppression of the purgative action of rhein anthrone, the active metabolite of sennosides A and B, by indomethacin in rats.
Rhein anthrone (12.48 mg kg-1) produces watery and mucoid diarrhoea approximately 20 min after intracaecal administration to rats. Pretreatment with the prostaglandin (PG) biosynthesis inhibitor indomethacin (10 mg kg-1, i.p.) only delayed and did not completely block the onset of the induced diarrhoea. Rhein anthrone stimulated PGE2 release into the rat colonic lumen and the increased release was depressed by indomethacin. Rhein anthrone also accelerated large intestinal transit and this acceleration could be partly inhibited by indomethacin, which was probably responsible for the delay in the onset of diarrhoea. Indomethacin prevented the enhanced water, K+ and mucus secretion and the reduced Na+ absorption in the colon which were induced by rhein anthrone. The net water secretion could not be reversed to net absorption and the mucus secretion was only slightly depressed by indomethacin. Thus, our findings suggest that other mechanisms, together with the PG-dependent mechanism, are involved in the purgative action of rhein anthrone in rats.
Yagi
T
T
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
Miyawaki
Y
Y
Nishikawa
A
A
Yamauchi
K
K
Kuwano
S
S
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D000880:Anthraquinones / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002400:Cathartics / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003106:Colon / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D015232:Dinoprostone / Q000378:metabolism; D004573:Electrolytes / Q000378:metabolism; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D009093:Mucus / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012676:Senna Extract; D000081226:Sennosides; D014867:Water / Q000378:metabolism; D000095322:Anthrones
D000873:Anthracenes; D000880:Anthraquinones; D002400:Cathartics; D015232:Dinoprostone; D004573:Electrolytes; D007213:Indomethacin; D012676:Senna Extract; D000081226:Sennosides; D014867:Water; C055876:rhein-9-anthrone; D000095322:Anthrones