Septide but not substance P stimulates inhibitory neurons in guinea-pig ileum

Recent evidence suggests that [pGlu6,Pro9]substance P-(6-11) (septide) may act on unusual tachykinin receptors. Here, we investigated the mechanisms of action of septide and other agonists acting on tachykinin NK1 receptors, in the guinea-pig ileum. Responses to septide but not to substance P or [Sar9,Met(O2)11]substance P were significantly (P < 0.01) potentiated by 1 microM tetrodotoxin. The data suggest that septide not only acts directly on smooth muscle tachykinin receptors to produce contraction, but also stimulates another receptor subtype on myenteric neurons to release inhibitory substance(s).