Stimulation and inhibition of gastrointestinal propulsion induced by substance P and substance K in the rat

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Abstract
1 Substance P and substance K (neurokinin A) (dose range: 0.08–80 nmol kg−1) were tested for their effects on gastrointestinal propulsion in the rat. The peptides were given by intraperitoneal injection concurrently with the intragastric administration of a test meal containing charcoal and 51Cr. 2 Examination 3 min after the test meal showed that high doses of substance P (> 0.74 nmol kg−1) and substance K (> 8.8 nmol kg−1) inhibited gastric emptying and gastrointestinal transit. This inhibitory effect was changed to a stimulant effect by pretreatment of the rats with atropine (3.5 μmol kg−1). Guanethidine pretreatment (67 μmol kg−1) revealed a facilitatory effect of low doses of the two tachykinins (about 1 nmol kg−1) on gastrointestinal propulsion. 3 Examination 15 min after the test meal demonstrated that substance P (> 0.74 nmol kg−1) dose-dependently enhanced gastrointestinal propulsion, an effect that was also seen after atropine pretreatment. Low doses of substance K (about 1 nmol kg−1) also stimulated gastrointestinal propulsion but this effect was abolished by atropine. In addition, atropine pretreatment revealed a stimulant effect of high doses of substance K (88 nmol kg−1) on gastric emptying. 4 These results show that the effects of substance P and substance K on gastrointestinal propulsion vary with dose and time and involve, at least partly, activation of the autonomic nervous system.