INHIBITION BY SUBSTANCE P OF SOME PERIPHERAL ACTIONS OF ACETYLCHOLINE IN THE CAT

Article date: August 1982

By: S.L. CLARK, R.W. RYALL in Volume 76, Issue 4, pages 595-602

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.

Substance P (2–20 nmol) injected into the lingual artery giving estimated concentrations in arterial blood of 10−6 to 10−5m, or intravenously giving estimated concentrations in blood of 10−8 to 10−7m, reduced hexamethonium‐sensitive but not atropine‐sensitive responses.

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.

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.

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.

There was desensitization to all of these effects of substance P which probably contributed to the variation in the magnitude of the effects observed.

Substance P had no effect on muscarinic actions of acetyl‐β‐methylcholine on the nictitating membrane or blood pressure.

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.

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.

Substance P (2–20 nmol) injected into the lingual artery giving estimated concentrations in arterial blood of 10−6 to 10−5m, or intravenously giving estimated concentrations in blood of 10−8 to 10−7m, reduced hexamethonium‐sensitive but not atropine‐sensitive responses.

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.

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.

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.

There was desensitization to all of these effects of substance P which probably contributed to the variation in the magnitude of the effects observed.

Substance P had no effect on muscarinic actions of acetyl‐β‐methylcholine on the nictitating membrane or blood pressure.

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.

DOI: 10.1111/j.1476-5381.1982.tb09259.x

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