A specific substance P antagonist attenuates non-cholinergic electrically induced contractures of the guinea pig isolated ileum.

The substance P (SP) analog, D-Pro2,D-Tryp7,9-SP attenuated in a dose-dependent fashion non-cholinergic excitatory responses of the guinea pig ileum to the exogenous administration of SP, but did not affect the atropine-resistant contractures produced by serotonin (1 microM), histamine (1 microM), bradykinin (0.01 microM) or prostaglandin F2 alpha (10 microM). Pretreatment with D-Pro2,D-Tryp7,9-SP also significantly reduced the magnitude of the non-cholinergic contracture evoked by field stimulation at 20 Hz. These results suggest that enteric SP-containing neurons can function in an efferent motor capacity to bring about non-cholinergic excitation of the longitudinal muscle layer of the guinea pig small bowel.