MODULATION OF PERISTALSIS BY NEUROTENSIN IN ISOLATED GUINEA-PIG INTESTINAL SEGMENTS

Neurotensin (1-100 nM) produced an inhibitory effect and an excitatory effect on the peristaltic activity elicited by intraluminal distensio n using the Trendelenburg method or the intraluminal perfusion method in isolated segments of guinea-pig small intestine. The relative contr ibution of these effects to the overall effect varied from one region to another of the small intestine. In the Trendelenburg preparation, t he excitatory effect was found to be accompanied by a decrease in the threshold intraluminal pressure required to trigger a peristaltic refl ex. A substantial difference between the jejunum and the ileum was not ed in that neurotensin-induced stimulation of peristaltic activity was observed in a smaller number of the segments in the jejunum than in t he ileum. A nonpeptide neurotensin receptor antagonist, SR 48692, nyla mino]tricyclo(3.3.1.1.(3.7))decan-2-carboxylic acid (90 nM), abolished both the inhibitory and excitatory effects. Apamin (10 nM) abolished the inhibitory effect. From these results, neurotensin appears to exer t both excitatory and inhibitory actions, via its receptors sensitive to SR 48692, on peristaltic activity in guinea-pig small intestine. Th e excitatory action varies with an increasing gradient toward the term inal end of the small intestine, and the inhibitory action involves ap amin-sensitive mechanism.