A DOPAMINE D-3 RECEPTOR AGONIST, 7-HYDROXY-N,N-DI-N-PROPYL-2-AMINOTETRALIN REDUCES GASTRIC-ACID AND PEPSIN-SECRETION AND EXPERIMENTAL GASTRIC-MUCOSAL INJURY IN RATS

Dopamine D-1/DA(1) agonists are associated with significant gastroprot ective and antisecretory effects. The new dopamine DA(3) agonist, 7-hy droxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT), possesses neural and behavioral properties that are similar to those of DA(1) agonists. In the present experiments, the effects of 7-OHDPAT on gastric acid secr etion in conscious and anaesthetized rats, on restraint stress-induced gastric mucosal injury and on gastric adherent mucus levels were exam ined. 7-OHDPAT (2.5, 5.0 and 10.0 mg/kg) reduced significantly basal g astric acid secretion in conscious rats (66%, 92% and 78% inhibition, respectively). 7-OHDPAT also reduced significantly gastric acid and pe psin secretion in pylorus-ligated rats. 7-OHDPAT reduced stress-induce d gastric mucosal injury at doses of 1.0, 5.0 and 10.0 mg/kg. Gastric adherent mucus was preserved only at the 5.0 mg/kg dose. Neither pretr eatment with the DA(1) antagonist, SCH23390, nor with the DA(2) antago nist, eticlopride, affected 7-OHDPAT-induced reductions in gastric sec retion or gastric mucosal injury. Although dopamine DA(3) receptors ex hibit greater amino acid sequence homology with DA(2) receptors than w ith DA(1) receptors, the possibility nevertheless exists that some of the gastrointestinal actions of dopamine and its agonists - both anti- secretory and gastroprotective - may be exerted through activation of DA(3) receptors.