5-HT3 receptor involvement in descending reflex relaxation in the rabbit isolated distal colon

In whole segments of rabbit distal colon with mucosa removed, descending reflex relaxations of the circular muscle (descending inhibition) elicited by inflating (0.1-1 ml) an intraluminal balloon, were partially antagonized by 100 microM hexamethonium and the 5-HT3 receptor antagonist, ondansetron (3 microM), and abolished by 1 microM tetrodotoxin. The inhibitory effects of hexamethonium and ondansetron were additive. Conversely, hexamethonium (100 microM) and ondansetron (3 microM) failed to reduce electrically induced non-adrenergic non-cholinergic (NANC) relaxations of colonic circular muscle. It is concluded that interneuronally released acetylcholine and 5-hydroxytryptamine (5-HT) activate descending inhibitory pathways supplying the circular coat, via nicotinic and 5-HT3 receptors, respectively. This evidence suggests a functional involvement of 5-hydroxytryptaminergic transmission in the descending inhibition of rabbit colon.