Evidence for functional NK1-tachykinin receptors on motor neurones supplying the circular muscle of guinea-pig small and large intestine

The guinea-pig intestine was investigated to determine which neurones are e xcited via NK1 receptors. The specific NK1 receptor agonists [Sar(9), Met(O -2)(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 w ere larger when nerve impulses were blocked with TTX, indicating that the a gonists excited inhibitory motor neurones. In the duodenum and ileum, TTX r educed agonist-evoked contractions indicating that excitatory motor neurone s were activated. In the presence of indomethacin, TTX enhanced contraction s of ileal circular muscle evoked by these agonists suggesting that NK1 rec eptors were on inhibitory motor neurones. Blockade of nitric oxide synthase (NOS) enhanced NK1 receptor agonist evoked contractions of duodenal circul ar muscle, indicating that the agonists excite inhibitory motor neurones in duodenum. Neurones immunoreactive for NK1 receptors were studied in the du odenum and distal colon. As reported previously for the ileum,(1) some neur ones were immunoreactive for NOS and had Dogiel type I morphology; features characteristic of inhibitory motor neurones. In conclusion, there are func tional NK1 receptors on excitatory and inhibitory motor neurones in the gui nea-pig small intestine and on inhibitory motor neurones in the colon.