Inhibition by substance P of some peripheral actions of acetylcholine in the cat.

1 The effect of substance P on contractions of the nictitating membrane and pressor responses to acetylcholine (ACh) and dimethylphenyl-piperazinium (DMPP) which were mediated via nocotinic receptors was studied in cats anaesthetized with chloralose.2 Substance P (2-20 nmol) injected into the lingual artery giving estimated concentrations in arterial blood of 10(-6) to 10(-5) M, or intravenously giving estimated concentrations in blood of 10(-8) to 10(-7) M, reduced hexamethonium-sensitive but not atropine-sensitive responses.3 The pressor effects of ACh and DMPP injected intra-arterially in atropinized and non-atropinized cats respectively were consistently attenuated by substance P given intra-arterially or intravenously.4 The contractile effect of ACh in atropinized and of DMPP in non-atropinized cats was attenuated by substance P injected intra-arterially but only rarely when the polypeptide was injected intravenously.5 The depressor effects of substance P per se were variable in magnitude and duration as were the inhibitory effects upon nicotinic receptors. The depressor and inhibitory effects of substance P were unrelated.6 There was desensitization to all of these effects of substance P which probably contributed to the variation in the magnitude of the effects observed.7 Substance P had no effect on muscarinic actions of acetyl-beta-methylcholine on the nictitating membrane or blood pressure.8 The results are discussed in relation to the ubiquity of the modulatory actions of substance P on nicotinic receptors and in relation to the possible physiological significance of the action.