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

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. Examination 3 min after the test meal showed that high doses of substance P (greater than 0.74 nmol kg-1) and substance K (greater than 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 mumol kg-1). Guanethidine pretreatment (67 mumol kg-1) revealed a facilitatory effect of low doses of the two tachykinins (about 1 nmol kg-1) on gastrointestinal propulsion. Examination 15 min after the test meal demonstrated that substance P (greater than 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. 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.