The time course of the spasmogenic effect of substance P (SP) on the longitudinal muscle (LM) of the guinea-pig ileum was investigated. Maximum effective concentrations of SP (greater than or equal to 10 ng/ml) produced a fast initial response which subsequently declined to about 50% of the initial contraction. This remaining half-maximum contraction was increased by physostigmine and decreased by tropicamide, morphine, and tetrodotoxin; hexamethonium had no effect. The results indicate that SP, apart from its direct action on the LM, also activates cholinergic neurones innervating the LM.
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