Rapid degradation of [3H]‐substance P in guinea‐pig ileum and rat vas deferens in vitro

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Abstract
1 The degradation of [3H]-substance P was monitored in guinea-pig ileum and rat vas deferens. Substantial and rapid metabolism occurred in both tissues within the time course of the pharmacological responses; for example, after 1 min more than 50% of the extracted tritium from both tissues was present in the form of metabolites. 2 [3H]-inulin was used to estimate the rate of equilibration of the extracellular space of guinea-pig ileum longitudinal muscle and rat vas deferens with the bath fluid; half-lives of 30 s and 5 min respectively were observed. 3 These two factors combine to give different concentrations of substance P in the biophase of the tissues. The peak concentration of substance P reached in the guinea-pig ileum longitudinal muscle was approximately five times higher than in the rat vas deferens. 4 An analogue of substance P, [3H]-DiMe-C7, was found to be stable in both tissues. 5 These results are discussed in the light of the suggested existence of multiple receptors for substance P, based on agonist potency differences.