A dopamine D3 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 D1/DA1 agonists are associated with significant gastroprotective and antisecretory effects. The new dopamine DA3 agonist, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OHDPAT), possesses neural and behavioral properties that are similar to those of DA1 agonists. In the present experiments, the effects of 7-OHDPAT on gastric acid secretion in conscious and anaesthetized rats, on restraint stress-induced gastric mucosal injury and on gastric adherent mucus levels were examined. 7-OHDPAT (2.5, 5.0 and 10.0 mg/kg) reduced significantly basal gastric acid secretion in conscious rats (66%, 92% and 78% inhibition, respectively). 7-OHDPAT also reduced significantly gastric acid and pepsin secretion in pylorus-ligated rats. 7-OHDPAT reduced stress-induced 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 pretreatment with the DA1 antagonist, SCH23390, nor with the DA2 antagonist, eticlopride, affected 7-OHDPAT-induced reductions in gastric secretion or gastric mucosal injury. Although dopamine DA3 receptors exhibit greater amino acid sequence homology with DA2 receptors than with DA1 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 DA3 receptors.
Glavin
G B
GB
Department of Pharmacology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000293:injuries / Q000378:metabolism*; D008297:Male; D010434:Pepsin A / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000503:physiopathology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D013764:Tetrahydronaphthalenes; D010434:Pepsin A; C031349:7-hydroxy-2-N,N-dipropylaminotetralin