Effects of dopamine on gastric mucosal lesions induced by ethanol in rats. Possible involvement of antigastric motor activity mediated with alpha 2-adrenoceptors.
Acidified ethanol (60% ethanol in 150 mM HCl, per os) induced elongated bands of hemorrhagic lesions along the long axis of the stomach within 1 hr in rats. Pretreatment with dopamine hydrochloride (DA: 1-10 mg/kg, subcutaneously) dose-dependently reduced the severity of these lesions. In parallel study, DA had no effect on acid secretion but inhibited gastric motor activity in a dose-related manner. The inhibitory effects of DA on both acidified ethanol-induced lesions and gastric motor activity were significantly reversed by pretreatment with yohimbine, an inhibitor of alpha 2-adrenoceptors (5 mg/kg, subcutaneously), but not by prazosin, haloperidol, or indomethacin. Similar to DA, both norepinephrine (NE: 1 mg/kg, subcutaneously) and epinephrine (EPI: 1 mg/kg, subcutaneously) showed inhibition of the motor activity and gastroprotection against acidified ethanol, but these effects were also significantly attenuated by yohimbine. A highly significant relationship was found between the inhibitory effects of DA, NE, and EPI on the motor activity and the mucosal lesions (r = 0.8577, P less than 0.05). In addition, administration of gentian violet (0.5% w/v, per os) stained the mucosa deep blue as elongated wide bands in the corpus region, and such localized staining was significantly prevented by DA, suggesting a flattening of the mucosal foldings in the presence of DA. These results suggest that DA (and other catecholamines) protects the rat gastric mucosa against injury caused by acidified ethanol, probably through inhibition of gastric motor activity mediated with stimulation of alpha 2-adrenoceptors.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nishiwaki
H
H
Okabe
S
S
D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013194:Staining and Labeling
D002395:Catecholamines; D011942:Receptors, Adrenergic, alpha; D000431:Ethanol; D004298:Dopamine