Aims: 

The role of tachykinins and their receptors in the regulation of gastrointestinal functions has been investigated for a long time. Substance P (SP), the most widely studied tachykinin, has been shown to modulate gastrointestinal motility. Despite the large number of studies about the effects of SP in the intestines, only few contradictory data are available about the effect of SP on the gastric contractions. The aim of our study was to analyze the effect of peripherally injected SP on the gastric motor activity in anesthetized rats.

Methods: 

We used the rubber balloon method. After 24 hours starvation Male Wistar rats (250–350g) were anesthetized with urethane (1.25g/kg ip.), and a rubber balloon was introduced orally into the stomach. Compounds were given intravenously (i.v.).

Results: 

1) SP at a lower dose range (74-7400 pmol/kg i.v.) induced a biphasic effect on the gastric motility, namely a transient relaxation followed by an increased gastric tone and phasic contractions. In contrast, higher doses (74-740 nmol/kg i.v.) induced only a more pronounced relaxant effect. 2) Pre-treatment with the NK1-receptor antagonist L-733,060 (11 mmol/kg i.v.) significantly decreased both the inhibitory and stimulatory effects of SP (74 pmol/kg). 3) Bilateral cervical vagotomy and pretreatment with atropine (1.4 mmol/kg i.v.) reduced the effect of SP as well. 4) Naloxone (11 mmol/kg i.v.) did not influence the effect of SP on the gastric motility.

Conclusions: 

Our results indicate that peripherally injected SP induces a biphasic effect on the gastric motility, which is (at least partly) mediated by NK1-receptors and vagal activation. In contrast, endogenous opioids are not involved in the effect of SP.

Support: 

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