The role of constitutive and inducible nitric oxide synthase in senna- and cascara-induced diarrhoea in the rat.
The role of constitutive and inducible nitric oxide (NO) synthase in rats treated with senna and cascara was studied. Senna (60 mg/kg p.o.) and cascara (800 mg/kg p.o.) ex vivo significantly increased Ca(2+)-dependent constitutive NO synthase activity in the rat colon. Induction of NO synthase (12% of the total NO synthase) was associated with cascara, but not senna, administration. Dexamethasone (0.03-0.3 mg/kg i.p.), which inhibits the expression of inducible NO synthase, significantly and dose-dependently reduced cascara-(but not senna-) induced diarrhoea and colonic fluid secretion. These findings suggest that senna probably exerts its laxative effect through stimulation of the constitutive isoform of NO synthase, while the inducible isoform of NO synthase also seems to be involved in the laxative effect of cascara.
Izzo
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Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Sautebin
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Rombolà
L
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Capasso
F
F
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002400:Cathartics / Q000008:administration & dosage / Q000633:toxicity*; D003106:Colon / Q000187:drug effects* / Q000201:enzymology; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced* / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007274:Injections, Intraperitoneal; D007408:Intestinal Absorption / Q000187:drug effects; D007527:Isoenzymes; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D031955:Rhamnus / Q000008:administration & dosage / Q000633:toxicity*; D012676:Senna Extract / Q000008:administration & dosage / Q000633:toxicity*; D014867:Water / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002400:Cathartics; D007527:Isoenzymes; D014867:Water; D003907:Dexamethasone; D012676:Senna Extract; D019001:Nitric Oxide Synthase