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The guinea-pig intestine was investigated to determine which neurones are excited via NK1 receptors. The specific NK1 receptor agonists [Sar9, Met(O2)11]-SP and septide contracted the circular muscle of all regions via a tetrodotoxin (TTX)-insensitive mechanism. In the proximal colon, they also evoked a TTX-sensitive relaxation; in the distal colon, the contractions were larger when nerve impulses were blocked with TTX, indicating that the agonists excited inhibitory motor neurones. In the duodenum and ileum, TTX reduced agonist-evoked contractions indicating that excitatory motor neurones were activated. In the presence of indomethacin, TTX enhanced contractions of ileal circular muscle evoked by these agonists suggesting that NK1 receptors were on inhibitory motor neurones. Blockade of nitric oxide synthase (NOS) enhanced NK1 receptor agonist evoked contractions of duodenal circular muscle, indicating that the agonists excite inhibitory motor neurones in duodenum. Neurones immunoreactive for NK1 receptors were studied in the duodenum and distal colon. As reported previously for the ileum,1 some neurones were immunoreactive for NOS and had Dogiel type I morphology; features characteristic of inhibitory motor neurones. In conclusion, there are functional NK1 receptors on excitatory and inhibitory motor neurones in the guinea-pig small intestine and on inhibitory motor neurones in the colon.