Morphine contracts the guinea pig ileal circular muscle by interfering with a nitric oxide mediated tonic inhibition

The effect of morphine was examined on the circular muscle of guinea pig ileal segments in vitro, with special regard to its interaction with enteric nitric oxide (NO) releasing neurons. In the presence of atropine (10(-6) M), morphine (10(-6) M) caused tonic contraction (approximately 7% of the maximal spasm) which was reversed by naloxone (10(-6) M). Tetrodotoxin (TTX; 10(-6) M) also caused contraction (14% of maximum); morphine completely lost its effect in the presence of TTX. Likewise, the NO synthase inhibitor N(G)-nitro-L-arginine (L-NOARG, 10(-4) M) elicited a tonic circular muscle contraction (12% of maximum) and completely prevented the excitatory action of TTX or morphine. The NO donor sodium nitroprusside (10(-7) to 10(-4) M) caused relaxation. In longitudinally oriented preparations in the presence of atropine (10(-6) M), no change in tone was observed upon administration of morphine (10(-6) M), TTX (10(-6) M), or L-NOARG (10(-4) M). In the circular muscle in the absence of atropine, cholecystokinin octapeptide (CCK-8; 10(-9) M) evoked a tonic-phasic contractile response which spontaneously faded away within 3 min. L-NOARG (10(-4) M) failed to affect intensity or duration of the response to CCK-8. It is concluded that NO-releasing myenteric neurons exert a tonic inhibitory influence upon the circular, but not longitudinal muscle of the guinea pig ileum. Morphine and TTX probably contract the circular muscle by reducing the amount of NO released. A release of NO seems to play no role in the contractile effect of CCK-8 or in its spontaneous termination.