Role of nitric oxide, vasoactive intestinal polypeptide, and ATP in inhibitory neurotransmission in human jejunum

Michel M. Murr, Bruno M. Balsiger, Gianrico Farrugia, Michael G. Sarr

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background. Inhibitory neurotransmission in the human intestine is poorly understood. This study was undertaken to determine the role of nitric oxide (NO), adenosine triphosphate (ATP), and vasoactive intestinal polypeptide (VIP) in inhibitory neurotransmission in human jejunal circular muscle strips. Methods. In vitro response of precontracted (10-5 M substance P) normal human jejunal muscle strips to electric field stimulation (EFS) under adrenergic and cholinergic receptor blockade was evaluated. Selective neural blockade was obtained by the NO synthase inhibitor L-N(G)- nitroarginine methyl ester (L-NAME, 10-3 M), VIP receptor antagonist (4-Cl- D-Phe6Leu17-VIP, 10-7 M), P2 purinergic receptor blocker suramin (3 x 1014 M), or the calcium-dependent potassium channel blocker apamin (10-6 M). Force generated in response to EFS was quantitated and analyzed statistically. Results. Exogenous NO and ATP dose-dependently inhibited contractile activity and relaxed muscle strips with a concentration yielding a 50% effect (ED50) of 4.5 ± 2.9 x 10-6 M and 3.3 ± 1.3 x 10-4 M, respectively. EFS resulted in relaxation of precontracted muscle strips in all groups. When compared with controls, relaxation was decreased but not abolished by L-NAME (-0.12 ± 0.03 vs -0.33 ± 0.05, -0.07 ± 0.03 vs -0.34 ± 0.05, and 0.04 ± 0.03 vs -0.30 ± 0.04 at 2, 5, and 10 Hz, respectively, P < 0.011). D-NAME (inactive stereoisomer of L-NAME), 4-Cl-D-Phe6Leu17- VIP, suramin, and apamin did not alter EFS-induced relaxation. Conclusions. Inhibition of NO synthesis by L-NAME reduced the inhibitory response to EFS, whereas blocking ATP and VIP receptors or other effector pathways had no effect. Our findings indicate that although NO plays a predominant role in inhibitory neurotransmission in human jejunal circular muscle, another neurotransmitter(s) appears to be involved as well. These data may impact on understanding mechanisms of disorders of gut dysmotility.

Original languageEnglish (US)
Pages (from-to)8-12
Number of pages5
JournalJournal of Surgical Research
Volume84
Issue number1
DOIs
StatePublished - Jun 1 1999

Fingerprint

Vasoactive Intestinal Peptide
NG-Nitroarginine Methyl Ester
Jejunum
Synaptic Transmission
Electric Stimulation
Nitric Oxide
Adenosine Triphosphate
Apamin
Suramin
Muscles
Purinergic P2 Receptor Antagonists
Potassium Channel Blockers
Calcium-Activated Potassium Channels
Stereoisomerism
Muscle Relaxation
Cholinergic Receptors
Substance P
Nitric Oxide Synthase
Adrenergic Receptors
Intestines

Keywords

  • Human smooth muscle
  • Inhibitory neurotransmission
  • Nitric oxide
  • Smooth muscle contractility
  • Vasoactive intestinal polypeptide ATP

ASJC Scopus subject areas

  • Surgery

Cite this

Role of nitric oxide, vasoactive intestinal polypeptide, and ATP in inhibitory neurotransmission in human jejunum. / Murr, Michel M.; Balsiger, Bruno M.; Farrugia, Gianrico; Sarr, Michael G.

In: Journal of Surgical Research, Vol. 84, No. 1, 01.06.1999, p. 8-12.

Research output: Contribution to journalArticle

@article{c33c1e12dc674346b5af9b06295de8a7,
title = "Role of nitric oxide, vasoactive intestinal polypeptide, and ATP in inhibitory neurotransmission in human jejunum",
abstract = "Background. Inhibitory neurotransmission in the human intestine is poorly understood. This study was undertaken to determine the role of nitric oxide (NO), adenosine triphosphate (ATP), and vasoactive intestinal polypeptide (VIP) in inhibitory neurotransmission in human jejunal circular muscle strips. Methods. In vitro response of precontracted (10-5 M substance P) normal human jejunal muscle strips to electric field stimulation (EFS) under adrenergic and cholinergic receptor blockade was evaluated. Selective neural blockade was obtained by the NO synthase inhibitor L-N(G)- nitroarginine methyl ester (L-NAME, 10-3 M), VIP receptor antagonist (4-Cl- D-Phe6Leu17-VIP, 10-7 M), P2 purinergic receptor blocker suramin (3 x 1014 M), or the calcium-dependent potassium channel blocker apamin (10-6 M). Force generated in response to EFS was quantitated and analyzed statistically. Results. Exogenous NO and ATP dose-dependently inhibited contractile activity and relaxed muscle strips with a concentration yielding a 50{\%} effect (ED50) of 4.5 ± 2.9 x 10-6 M and 3.3 ± 1.3 x 10-4 M, respectively. EFS resulted in relaxation of precontracted muscle strips in all groups. When compared with controls, relaxation was decreased but not abolished by L-NAME (-0.12 ± 0.03 vs -0.33 ± 0.05, -0.07 ± 0.03 vs -0.34 ± 0.05, and 0.04 ± 0.03 vs -0.30 ± 0.04 at 2, 5, and 10 Hz, respectively, P < 0.011). D-NAME (inactive stereoisomer of L-NAME), 4-Cl-D-Phe6Leu17- VIP, suramin, and apamin did not alter EFS-induced relaxation. Conclusions. Inhibition of NO synthesis by L-NAME reduced the inhibitory response to EFS, whereas blocking ATP and VIP receptors or other effector pathways had no effect. Our findings indicate that although NO plays a predominant role in inhibitory neurotransmission in human jejunal circular muscle, another neurotransmitter(s) appears to be involved as well. These data may impact on understanding mechanisms of disorders of gut dysmotility.",
keywords = "Human smooth muscle, Inhibitory neurotransmission, Nitric oxide, Smooth muscle contractility, Vasoactive intestinal polypeptide ATP",
author = "Murr, {Michel M.} and Balsiger, {Bruno M.} and Gianrico Farrugia and Sarr, {Michael G.}",
year = "1999",
month = "6",
day = "1",
doi = "10.1006/jsre.1999.5590",
language = "English (US)",
volume = "84",
pages = "8--12",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Role of nitric oxide, vasoactive intestinal polypeptide, and ATP in inhibitory neurotransmission in human jejunum

AU - Murr, Michel M.

AU - Balsiger, Bruno M.

AU - Farrugia, Gianrico

AU - Sarr, Michael G.

PY - 1999/6/1

Y1 - 1999/6/1

N2 - Background. Inhibitory neurotransmission in the human intestine is poorly understood. This study was undertaken to determine the role of nitric oxide (NO), adenosine triphosphate (ATP), and vasoactive intestinal polypeptide (VIP) in inhibitory neurotransmission in human jejunal circular muscle strips. Methods. In vitro response of precontracted (10-5 M substance P) normal human jejunal muscle strips to electric field stimulation (EFS) under adrenergic and cholinergic receptor blockade was evaluated. Selective neural blockade was obtained by the NO synthase inhibitor L-N(G)- nitroarginine methyl ester (L-NAME, 10-3 M), VIP receptor antagonist (4-Cl- D-Phe6Leu17-VIP, 10-7 M), P2 purinergic receptor blocker suramin (3 x 1014 M), or the calcium-dependent potassium channel blocker apamin (10-6 M). Force generated in response to EFS was quantitated and analyzed statistically. Results. Exogenous NO and ATP dose-dependently inhibited contractile activity and relaxed muscle strips with a concentration yielding a 50% effect (ED50) of 4.5 ± 2.9 x 10-6 M and 3.3 ± 1.3 x 10-4 M, respectively. EFS resulted in relaxation of precontracted muscle strips in all groups. When compared with controls, relaxation was decreased but not abolished by L-NAME (-0.12 ± 0.03 vs -0.33 ± 0.05, -0.07 ± 0.03 vs -0.34 ± 0.05, and 0.04 ± 0.03 vs -0.30 ± 0.04 at 2, 5, and 10 Hz, respectively, P < 0.011). D-NAME (inactive stereoisomer of L-NAME), 4-Cl-D-Phe6Leu17- VIP, suramin, and apamin did not alter EFS-induced relaxation. Conclusions. Inhibition of NO synthesis by L-NAME reduced the inhibitory response to EFS, whereas blocking ATP and VIP receptors or other effector pathways had no effect. Our findings indicate that although NO plays a predominant role in inhibitory neurotransmission in human jejunal circular muscle, another neurotransmitter(s) appears to be involved as well. These data may impact on understanding mechanisms of disorders of gut dysmotility.

AB - Background. Inhibitory neurotransmission in the human intestine is poorly understood. This study was undertaken to determine the role of nitric oxide (NO), adenosine triphosphate (ATP), and vasoactive intestinal polypeptide (VIP) in inhibitory neurotransmission in human jejunal circular muscle strips. Methods. In vitro response of precontracted (10-5 M substance P) normal human jejunal muscle strips to electric field stimulation (EFS) under adrenergic and cholinergic receptor blockade was evaluated. Selective neural blockade was obtained by the NO synthase inhibitor L-N(G)- nitroarginine methyl ester (L-NAME, 10-3 M), VIP receptor antagonist (4-Cl- D-Phe6Leu17-VIP, 10-7 M), P2 purinergic receptor blocker suramin (3 x 1014 M), or the calcium-dependent potassium channel blocker apamin (10-6 M). Force generated in response to EFS was quantitated and analyzed statistically. Results. Exogenous NO and ATP dose-dependently inhibited contractile activity and relaxed muscle strips with a concentration yielding a 50% effect (ED50) of 4.5 ± 2.9 x 10-6 M and 3.3 ± 1.3 x 10-4 M, respectively. EFS resulted in relaxation of precontracted muscle strips in all groups. When compared with controls, relaxation was decreased but not abolished by L-NAME (-0.12 ± 0.03 vs -0.33 ± 0.05, -0.07 ± 0.03 vs -0.34 ± 0.05, and 0.04 ± 0.03 vs -0.30 ± 0.04 at 2, 5, and 10 Hz, respectively, P < 0.011). D-NAME (inactive stereoisomer of L-NAME), 4-Cl-D-Phe6Leu17- VIP, suramin, and apamin did not alter EFS-induced relaxation. Conclusions. Inhibition of NO synthesis by L-NAME reduced the inhibitory response to EFS, whereas blocking ATP and VIP receptors or other effector pathways had no effect. Our findings indicate that although NO plays a predominant role in inhibitory neurotransmission in human jejunal circular muscle, another neurotransmitter(s) appears to be involved as well. These data may impact on understanding mechanisms of disorders of gut dysmotility.

KW - Human smooth muscle

KW - Inhibitory neurotransmission

KW - Nitric oxide

KW - Smooth muscle contractility

KW - Vasoactive intestinal polypeptide ATP

UR - http://www.scopus.com/inward/record.url?scp=0033150232&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033150232&partnerID=8YFLogxK

U2 - 10.1006/jsre.1999.5590

DO - 10.1006/jsre.1999.5590

M3 - Article

C2 - 10334881

AN - SCOPUS:0033150232

VL - 84

SP - 8

EP - 12

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 1

ER -