Vasodilatation of arterioles by acetylcholine released from single neurones in the guinea-pig submucosal plexus

T. O. Neild, Ke-Zhong Shen, A. Surprenant

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Abstract

The nervous control of arterioles in the guinea-pig submucosal plexus was studied. Outside diameters of arterioles were recorded using a video-monitoring system. Changes in arteriolar diameter in response to electrical stimulation of single neurones or ganglia in the plexus were measured. When the arteriole was pre-constricted with the prostaglandin analogue U46619 or with phenylephrine, electrical stimulation (2-20 Hz, 10 s) of a ganglion dilated the blood vessel. This vasodilatation was abolished by tetrodotoxin or by cutting the fine nerve strands running between the ganglion and the arteriole. The vasodilatations caused by ganglionic stimulation were blocked by the muscarinic antagonists atropine, pirenzepine, (11[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H- pyrido[2,3-b][1,4]benzodiazepine-6)-one (AFDX-116), 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) and hexahydrosilodifenidol (HSDF). IC50 values for the inhibition of nerve-evoked vasodilatation by pirenzepine, AFDX-116 and HSDF were 500 nM, 4 μM and 25 nM respectively. Physostigmine (1 μM) increased the dilatation by 90%. Muscarine dilated all submucosal arterioles; the concentration causing half-maximum effects was 200 nM. Muscarinic vasodilatations were inhibited by pirenzepine, AFDX-116, and HSDF in a competitive manner; dissociation equilibrium constants determined by Schild analyses were 125 nM, 1.3 μM and 4 nM respectively. Gossypol, an irreversible inhibitor of the production of endothelium-derived relaxing factor (EDRF), did not reduce the vasodilatation produced by either ganglionic stimulation or muscarine in submucosal arterioles. Intracellular recordings were made from submucosal neurones and action potentials were elicited by depolarizing current pulses (10 ms duration, 10 Hz/10 s). In seven neurones vasodilatation was associated with intracellularly evoked action potentials; this vasodilatation was blocked by pirenzepine. Cell bodies of reidentified vasodilator neurones were subsequently shown to contain immunoreactive choline acetyltransferase. These results show that cholinergic neurones in the submucosal plexus project to submucosal arterioles and that they release acetylcholine onto muscarinic receptors to produce vasodilatation. The muscarinic receptor activated by nerve-released acetylcholine is the M3 subtype and its location appears to be on the vascular smooth muscle rather than the endothelium.

Original languageEnglish (US)
Pages (from-to)247-265
Number of pages19
JournalJournal of Physiology
Volume420
StatePublished - 1990

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Submucous Plexus
Arterioles
Vasodilation
Acetylcholine
Guinea Pigs
Pirenzepine
Neurons
Ganglia
Muscarine
Muscarinic Receptors
Electric Stimulation
Action Potentials
Gossypol
Synthetic Prostaglandins
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Endothelium-Dependent Relaxing Factors
Physostigmine
Cholinergic Neurons
Muscarinic Antagonists
Choline O-Acetyltransferase

ASJC Scopus subject areas

  • Physiology

Cite this

Vasodilatation of arterioles by acetylcholine released from single neurones in the guinea-pig submucosal plexus. / Neild, T. O.; Shen, Ke-Zhong; Surprenant, A.

In: Journal of Physiology, Vol. 420, 1990, p. 247-265.

Research output: Contribution to journalArticle

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