Relationship between nitric oxide and platelet-activating factor in castor-oil induced mucosal injury in the rat duodenum.
The modulation of platelet activating factor (PAF) formation in duodenal tissue by nitric oxide (NO) released in response to castor oil was studied in rats pretreated with NG-nitro-L-arginine methyl ester (L-NAME, 6.25-25 mg/kg, i.p.), an inhibitor of NO synthase, NG-nitro-D-arginine methyl ester (D-NAME, 25 mg/kg, i.p.), the inactive enantiomer of L-NAME or isosorbide-5-mononitrate (IMN, 30-90 mg/kg, p.o.), a NO donating compound. Castor oil (2 ml/rat orally) increased PAF production in the rat duodenum 3 h after challenge. L-NAME, but not D-NAME, enhanced the amount of PAF formed by duodenal tissue, while IMN (30-90 mg/kg) counteracted the effects of L-NAME (12.5 mg/kg) and also reduced PAF release in the tissue of rats treated with castor oil. L-NAME 12.5 mg/kg, but not D-NAME, enhanced both macroscopic damage and acid phosphatase release induced by castor oil. These effects were reduced by a PAF antagonist BN 52021 (3-t-Butyl-hexahydro-4, 7b, 11-trihydroxy-8-methyl-9H-1, 7a-epoxymethano-1H, 6aH-cyclopenta [c] furo [2, 3b] furo [3'2':3,4] cyclopenta [1.2-d]furan-5,9,12(4H)trione) 10 and 20 mg/kg i.p. Such findings suggest that endogenous nitric oxide could reduce PAF biosynthesis in castor oil-treated rats.
Mascolo
N
N
Department of Experimental Pharmacology, School of Pharmacy, Naples, Italy.
Izzo
A A
AA
Gaginella
T S
TS
Capasso
F
F
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002368:Castor Oil / Q000009:adverse effects / Q000494:pharmacology*; D002400:Cathartics / Q000494:pharmacology*; D004234:Diuretics, Osmotic / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D007547:Isosorbide / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar
D002400:Cathartics; D004234:Diuretics, Osmotic; D010972:Platelet Activating Factor; D009569:Nitric Oxide; D002368:Castor Oil; D019001:Nitric Oxide Synthase; D000135:Acid Phosphatase; D019331:NG-Nitroarginine Methyl Ester; D007547:Isosorbide