Adenosine: a novel ulcer modulator in stomachs.
Adenosine has been demonstrated for its actions on gastric secretion and stress-induced gastric ulceration in animals. We examined the pharmacological actions of adenosine on ethanol-evoked gastric lesions and gastric mucosal blood flow (GMBF) in rats, because both of them are closely related. Adenosine pretreatment, in dose of 7.5 mg/kg increased GMBF and protected against ethanol-evoked gastric lesion formation. However, this antiulcer action was followed by an aggravation of gastric lesions and reduction in GMBF. We further investigated whether these actions could act through the adenosine A1 or A2 receptors, therefore L-phenylisopropyladenosine (L-PIA) or N-ethylcarboxamidoadenosine (NECA), the adenosine A1 or A2 receptor agonists, respectively, were used. The drugs given in doses of 10 or 50 micrograms/kg for L-PIA and 1 or 5 micrograms/kg for NECA, dose-dependently inhibited GMBF and potentiated ethanol-induced gastric damage. When the two drugs were given together to animals, they did not further aggravate the severity of ulceration and reduction of GMBF. These findings indicate that the antiulcer action of adenosine is not mediated via the adenosine A1 and A2 receptors but if acts through different adenosine receptor subtypes. It was because the lesion worsening effects of adenosine at the second stage of the biphasic responses were similar to the actions of L-PIA and NECA, the ulcer potentiating effect is probably acting through adenosine A1 and A2 receptors in anaesthetised rats.
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
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D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D004305:Dose-Response Relationship, Drug; D000431:Ethanol; D005753:Gastric Mucosa / Q000098:blood supply; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D014665:Vasodilator Agents / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D000431:Ethanol; D000241:Adenosine