Characterization of dopamine receptor subtypes involved in experimentally induced gastric and duodenal ulcers in rats.
There are conflicting reports about the role of dopamine in gastric and duodenal ulcers. This investigation was undertaken to characterize the specific subtypes of dopamine receptor involved in gastric and duodenal ulceration. Administration of dopamine D1 agonist fenoldopam and dopamine D2 antagonist sulpiride elicited a significant decrease in acid secretion, total acid output, pepsin output and histamine content in the gastric juice, and reduced ulcer-index values, in pylorus-ligated rats. However, dopamine D1 receptor antagonist SCH 39166 ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5H -benzo (d) naptho -(2,1-b) azepine) and the D2 receptor agonist quinpirole led to significant augmentation of these parameters compared with respective controls. In the restraint plus water-immersion stress model the score for intraluminal bleeding and the cumulative gastric lesion length was significantly lower for rats treated with fenoldopam and sulpiride. The opposite effects were observed after pretreatment of rats with SCH 39166 and quinpirole. In the cysteamine-induced duodenal ulcer model the mean ulcer area and the score for intensity were significantly lower for fenoldopam and sulpiride and higher for SCH 39166 and quinpirole. Our data suggest that the dopamine D1 and D2 receptors have opposite effects on gastric and duodenal ulcers. Whereas stimulation of dopamine D1 receptors inhibits the formation of gastric and duodenal ulcers, stimulation of dopamine D2 receptors has a pro-ulcerogenic effect.
Desai
J K
JK
Department of Pharmacology, L.M. College of Pharmacy, Navrangpura, Ahmedabad, India.
Goyal
R K
RK
Parmar
N S
NS
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D003543:Cysteamine / Q000009:adverse effects; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D018818:Fenoldopam / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism; D005750:Gastric Juice / Q000737:chemistry; D006471:Gastrointestinal Hemorrhage / Q000188:drug therapy / Q000209:etiology; D006632:Histamine / Q000378:metabolism; D007101:Immersion / Q000009:adverse effects; D008026:Ligation; D008297:Male; D010434:Pepsin A / Q000378:metabolism; D010437:Peptic Ulcer / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D011708:Pylorus; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D012149:Restraint, Physical / Q000009:adverse effects; D012720:Severity of Illness Index; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013469:Sulpiride / Q000494:pharmacology
D001552:Benzazepines; D001993:Bronchodilator Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C058081:ecopipam; D019257:Quinpirole; D003543:Cysteamine; D001285:Atropine; D013469:Sulpiride; D006632:Histamine; D010434:Pepsin A; D018818:Fenoldopam