INHIBITION OF ACID-INDUCED HYPEREMIA IN THE RAT STOMACH BY ENDOGENOUSNK2 RECEPTOR LIGANDS

Since exogenously applied tachykinins (substance P and neurokinin A) p revent the neurogenic hyperaemia which is elicited by acid back-diffus ion in the rat stomach, we investigated whether endogenous tachykinins would act in a similar manner. Acid back-diffusion, induced by perfus ing the stomach with 15% ethanol in the presence of 0.05 M HCl, increa sed gastric mucosal blood flaw (GMBF) by 60-100% as determined by hydr ogen clearance in urethane-anaesthetized rats. This response remained unchanged after pretreatment with the tachykinin NK1 receptor antagoni st SR 140,333 (300 nmol/kg) but tended to be enhanced by the NK2 recep tor antagonist MEN 10,627 (200 nmol/kg). When given during ongoing aci d back-diffusion, MEN 10,627 significantly enhanced the acid-evoked va sodilatation as compared with vehicle or SR 140,333. We conclude that endogenously released tachykinins, acting via NK2 receptors, limit the gastric hyperaemic response to acid. (C) 1997 Elsevier Science Irelan d Ltd.