Aims: 

Tachykinins play an important role in the regulation of gastrointestinal functions, however, in spite of the intensive studies, their role in the regulation of gastric mucosal integrity has not yet been completely clarified. Both aggravation of ethanol-induced mucosal damage and lack of effect have been reported after peripheral injection of substance P (SP) in rats, while central injection of SP reduced cold-restraint stress-induced gastric ulcers. The aim of our study was to analyze the effect of centrally injected SP in an acid-independent ulcer model in rats.

Methods: 

The ethanol-ulcer model was used. After 24 h starvation, male Wistar rats were given 0.5 ml acidified ethanol orally. The mucosal lesions were evaluated 1 h later. SP was given intracerebroventricularly (i.c.v.).

Results: 

1) SP (9.3–37 pmol/rat i.c.v.) dose-dependently inhibited the formation of ethanol-induced ulcers. 2) The protective effect of SP was inhibited by the NK1-receptor antagonist L-733,060 (1.1 nmol i.c.v.). 3) The non-selective opioid receptor antagonist naloxone (27 nmol i.c.v.) antagonized the effect of SP as well, while the k opioid receptor antagonist norbinaltorphimine (14 nmol i.c.v.) and the d opioid receptor antagonist naltrindole (5 nmol i.c.v.) had no effect. 4) Atropine (1.4 mmol/kg i.v.) and hexamethonium (37 mmol/kg i.v.) significantly reduced the effect of SP. 5) Inhibition of the peripheral prostaglandin- and NO-synthesis with indomethacin (56 mmol/kg per os) and L-NNA (13.7 mmol/kg i.v.) also abolished the protective effect of SP.

Conclusions: 

Our results suggest that SP induces central, vagally mediated gastroprotection in rats, and this effect is mediated by NK1-receptors and (at least partly) by endogenous opioids acting on m-opioid receptors. In the periphery both prostaglandins and NO are involved in the mediation of this effect.

Support: 

ETT 341/2009 from the Scientific Health Council and National Office for Research and Technology (NKTH)