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.
N1 - Funding Information:
1Supported by NIH RO1 DK39337 (M.G.S.) and the Mayo Foundation. 2Current address: University of South Florida, Department of Surgery, Tampa General Hospital, P.O. Box 1289, Tampa, FL 33601. 3To whom correspondence should be addressed. Fax: (507) 255– 6318.
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
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U2 - 10.1006/jsre.1999.5590
DO - 10.1006/jsre.1999.5590
M3 - Article
C2 - 10334881
AN - SCOPUS:0033150232
SN - 0022-4804
VL - 84
SP - 8
EP - 12
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 1
ER -