Myenteric 5-HT-containing neurones activate the descending cholinergic excitatory pathway to the circular muscle of guinea-pig ileum.

1. Participation of myenteric 5-hydroxytryptamine (5-HT)-containing neurones in the ascending and descending pathways of the guinea-pig isolated ileum was investigated in a new preparation. Transmural electrical stimulation of the longitudinal muscle-myenteric plexus (LM-MP) portion of the preparation caused ascending and descending contractions of circular or longitudinal muscle in the attached, intact segments situated orally or anally to the point of stimulation. 2. All contractions of LM-MP stimulation were abolished by tetrodotoxin (0.2 microM). The ascending and descending contractions of circular muscles were also abolished by atropine and inhibited to about 50% by hexamethonium. They were not affected by desensitization to substance P (SP) or by the SP antagonist, (D-Pro2,D-Trp7,9)-substance P. The contractions of longitudinal muscles were inhibited by about 45% by hexamethonium and abolished by a combination of atropine with SP desensitization or the SP antagonist, (D-Pro2,D-Trp7,9)-substance P. 3. Desensitization to 5-HT, ICS 205-930 (1 microM) or cocaine (1 microM) reduced the descending contraction of circular muscle by 80-90%, without significantly affecting the ascending contraction. Methysergide (0.2 microM) failed to alter either contraction. 4. 5-HT desensitization, ICS 205-930 and cocaine only partially reduced the descending contraction of longitudinal muscle. A similar reduction of the ascending contraction (20-30%) was also observed. Methysergide had no effects on either contraction. 5. Contractions of either circular or longitudinal muscle produced by field stimulation of the intact segment were not significantly affected by any of the 5-HT receptor antagonists tested. 6. The results imply that 5-HT-containing neurones, as interneurones, are involved mainly in the descending cholinergic excitatory pathway to the circular muscles.