Three gaseous neurotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide, are involved in the neurogenic relaxation responses of the porcine internal anal sphincter

Oladayo Folasire, Kylie A. Mills, Donna J. Sellers, Russ Chess-Williams

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6 Citations (Scopus)

Abstract

Background/Aims The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. Methods Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems. Results Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist, atropine (1 μM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 μM). Contractile responses were also reduced (by 45% at 5 Hz, P < 0.01) following desensitisation of purinergic receptors with a,β-methylene-ATP (10 μM). In the presence of guanethidine, atropine, and a,β-methylene-ATP, the remaining relaxatory responses to EFS were examined. These responses were not altered by the cyclooxygenase inhibitor, indomethacin (5 μM), the vasoactive intestinal polypeptide receptor antagonist, [D-p-Cl-Phe6, Leu17]- vasoactive intestinal peptide (PheLeu-VIP; 100 nM), or the purinoceptor antagonists, 8-phenyltheophyline (P1 receptors) or suramin (P2 receptors). However, relaxation responses were reduced by N?-nitro-L-arginine (L-NNA; 100 μM), an inhibitor of nitric oxide synthesis (40-50% reduction), zinc protoprophyrin IX (10 μM), an inhibitor of carbon monoxide synthesis (20-40% reduction), and also propargylglycine (30 μM) and aminooxyacetic acid (30 μM), inhibitors of hydrogen sulphide synthesis (15-20% reduction). Conclusions Stimulation of IAS efferent nerves releases excitatory and inhibitory neurotransmitters: noradrenaline is the predominant contractile transmitter with a smaller component from ATP, whilst 3 gases mediate relaxation responses to EFS, with the combined contributions being nitric oxide > carbon monoxide > hydrogen sulfide.

Original languageEnglish
Pages (from-to)141-148
Number of pages8
JournalJournal of Neurogastroenterology and Motility
Volume22
Issue number1
Early online date2015
DOIs
Publication statusPublished - 2016

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Hydrogen Sulfide
Anal Canal
Carbon Monoxide
Neurotransmitter Agents
Nitric Oxide
Swine
Electric Stimulation
Guanethidine
Adrenergic Neurons
Muscarinic Antagonists
Adrenergic Antagonists
Muscarinic Receptors
Atropine
carbon sulfide

Cite this

@article{170aa86ebbee468ba2853743895c323c,
title = "Three gaseous neurotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide, are involved in the neurogenic relaxation responses of the porcine internal anal sphincter",
abstract = "Background/Aims The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. Methods Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems. Results Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist, atropine (1 μM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 μM). Contractile responses were also reduced (by 45{\%} at 5 Hz, P < 0.01) following desensitisation of purinergic receptors with a,β-methylene-ATP (10 μM). In the presence of guanethidine, atropine, and a,β-methylene-ATP, the remaining relaxatory responses to EFS were examined. These responses were not altered by the cyclooxygenase inhibitor, indomethacin (5 μM), the vasoactive intestinal polypeptide receptor antagonist, [D-p-Cl-Phe6, Leu17]- vasoactive intestinal peptide (PheLeu-VIP; 100 nM), or the purinoceptor antagonists, 8-phenyltheophyline (P1 receptors) or suramin (P2 receptors). However, relaxation responses were reduced by N?-nitro-L-arginine (L-NNA; 100 μM), an inhibitor of nitric oxide synthesis (40-50{\%} reduction), zinc protoprophyrin IX (10 μM), an inhibitor of carbon monoxide synthesis (20-40{\%} reduction), and also propargylglycine (30 μM) and aminooxyacetic acid (30 μM), inhibitors of hydrogen sulphide synthesis (15-20{\%} reduction). Conclusions Stimulation of IAS efferent nerves releases excitatory and inhibitory neurotransmitters: noradrenaline is the predominant contractile transmitter with a smaller component from ATP, whilst 3 gases mediate relaxation responses to EFS, with the combined contributions being nitric oxide > carbon monoxide > hydrogen sulfide.",
author = "Oladayo Folasire and Mills, {Kylie A.} and Sellers, {Donna J.} and Russ Chess-Williams",
year = "2016",
doi = "10.5056/jnm15036",
language = "English",
volume = "22",
pages = "141--148",
journal = "Journal of Neurogastroenterology and Motility",
issn = "2093-0879",
publisher = "Korean Society of Neurogastroenterology and Motility",
number = "1",

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TY - JOUR

T1 - Three gaseous neurotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide, are involved in the neurogenic relaxation responses of the porcine internal anal sphincter

AU - Folasire, Oladayo

AU - Mills, Kylie A.

AU - Sellers, Donna J.

AU - Chess-Williams, Russ

PY - 2016

Y1 - 2016

N2 - Background/Aims The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. Methods Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems. Results Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist, atropine (1 μM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 μM). Contractile responses were also reduced (by 45% at 5 Hz, P < 0.01) following desensitisation of purinergic receptors with a,β-methylene-ATP (10 μM). In the presence of guanethidine, atropine, and a,β-methylene-ATP, the remaining relaxatory responses to EFS were examined. These responses were not altered by the cyclooxygenase inhibitor, indomethacin (5 μM), the vasoactive intestinal polypeptide receptor antagonist, [D-p-Cl-Phe6, Leu17]- vasoactive intestinal peptide (PheLeu-VIP; 100 nM), or the purinoceptor antagonists, 8-phenyltheophyline (P1 receptors) or suramin (P2 receptors). However, relaxation responses were reduced by N?-nitro-L-arginine (L-NNA; 100 μM), an inhibitor of nitric oxide synthesis (40-50% reduction), zinc protoprophyrin IX (10 μM), an inhibitor of carbon monoxide synthesis (20-40% reduction), and also propargylglycine (30 μM) and aminooxyacetic acid (30 μM), inhibitors of hydrogen sulphide synthesis (15-20% reduction). Conclusions Stimulation of IAS efferent nerves releases excitatory and inhibitory neurotransmitters: noradrenaline is the predominant contractile transmitter with a smaller component from ATP, whilst 3 gases mediate relaxation responses to EFS, with the combined contributions being nitric oxide > carbon monoxide > hydrogen sulfide.

AB - Background/Aims The internal anal sphincter (IAS) plays an important role in maintaining continence and a number of neurotransmitters are known to regulate IAS tone. The aim of this study was to determine the relative importance of the neurotransmitters involved in the relaxant and contractile responses of the porcine IAS. Methods Responses of isolated strips of IAS to electrical field stimulation (EFS) were obtained in the absence and presence of inhibitors of neurotransmitter systems. Results Contractile responses of the sphincter to EFS were unaffected by the muscarinic receptor antagonist, atropine (1 μM), but were almost completely abolished by the adrenergic neuron blocker guanethidine (10 μM). Contractile responses were also reduced (by 45% at 5 Hz, P < 0.01) following desensitisation of purinergic receptors with a,β-methylene-ATP (10 μM). In the presence of guanethidine, atropine, and a,β-methylene-ATP, the remaining relaxatory responses to EFS were examined. These responses were not altered by the cyclooxygenase inhibitor, indomethacin (5 μM), the vasoactive intestinal polypeptide receptor antagonist, [D-p-Cl-Phe6, Leu17]- vasoactive intestinal peptide (PheLeu-VIP; 100 nM), or the purinoceptor antagonists, 8-phenyltheophyline (P1 receptors) or suramin (P2 receptors). However, relaxation responses were reduced by N?-nitro-L-arginine (L-NNA; 100 μM), an inhibitor of nitric oxide synthesis (40-50% reduction), zinc protoprophyrin IX (10 μM), an inhibitor of carbon monoxide synthesis (20-40% reduction), and also propargylglycine (30 μM) and aminooxyacetic acid (30 μM), inhibitors of hydrogen sulphide synthesis (15-20% reduction). Conclusions Stimulation of IAS efferent nerves releases excitatory and inhibitory neurotransmitters: noradrenaline is the predominant contractile transmitter with a smaller component from ATP, whilst 3 gases mediate relaxation responses to EFS, with the combined contributions being nitric oxide > carbon monoxide > hydrogen sulfide.

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U2 - 10.5056/jnm15036

DO - 10.5056/jnm15036

M3 - Article

VL - 22

SP - 141

EP - 148

JO - Journal of Neurogastroenterology and Motility

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SN - 2093-0879

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