Interferon-inducer polyriboinosinic-polyribocytidylic acid: a potent anti-gastric ulcer agent and inhibitor of the gastric proton pump in rats.
1. Polyriboinosinic-polyribocytidylic acid (Poly I:Poly C), an interferon inducer was studied for its effect on gastric ulceration in rats. Polyriboinosinic-polyribocytidylic acid (1, 2 and 4 mg/kg, i.m.) showed a dose-dependent inhibition of gastric ulcers induced by aspirin, cold restraint stress and pylorus ligation (Shay's model). Protective dose (PD50) +/- SEM values of Poly I:Poly C on these models of ulcers were 1.9 +/- 0.2, 2.3 +/- 0.4 and 2.8 +/- 0.4 (mg/kg, i.m.) respectively. 2. Polyriboinosinic-polyribocytidylic acid (10-60 micrograms) produced dose-dependent inhibition of gastric proton pump (H+/K(+)-ATPase) activity in the gastric parietal microsomal fraction. The concentration of Poly I:Poly C causing a 50% inhibition (IC50) +/- SEM was found to be 17.6 +/- 1.2 micrograms. 3. Polyriboinosinic-polyribocytidylic acid caused a significant decrease in free and total acid and pepsin and an increase in mucin content in Shay (pylorus-ligated) rat. 4. Polyriboinosinic-polyribocytidylic acid did not exert a significant influence on isolated tissue preparations for anti-cholinergic (acetylcholine-induced contraction of guinea-pig ileum) and H2-anti-histaminic (histamine-induced contraction of rat uterus and guinea-pig auricle) activities. 5. Thus, the present study indicates that Poly I:Poly C may possess anti-gastric ulcer activity as a result of inhibition of the gastric proton pump.
Nath
C
C
Neuropharmacology Unit (Central Drug Research Institute), KG Medical College, Lucknow, India. noot@cscdri.ren.nic.in
Rastogi
L
L
Dikshit
M
M
Patnaik
G K
GK
Saxena
R C
RC
Gupta
M B
MB
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007369:Interferon Inducers / Q000494:pharmacology*; D008297:Male; D011070:Poly I-C / Q000494:pharmacology*; D054328:Proton Pump Inhibitors; D011708:Pylorus / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000517:prevention & control; D014590:Uterine Contraction / Q000187:drug effects
D000897:Anti-Ulcer Agents; D004791:Enzyme Inhibitors; D007369:Interferon Inducers; D054328:Proton Pump Inhibitors; D011070:Poly I-C