TY - JOUR
T1 - Evidence that nitric oxide is a non-adrenergic non-cholinergic inhibitory neurotransmitter in the circular muscle of the mouse distal colon
T2 - A study on the mechanism of nitric oxide-induced relaxation
AU - Nishiyama, Kazuhiro
AU - Azuma, Yasu Taka
AU - Shintaku, Kazuma
AU - Yoshida, Natsuho
AU - Nakajima, Hidemitsu
AU - Takeuchi, Tadayoshi
N1 - Publisher Copyright:
© 2014 S. Karger AG, Basel.
PY - 2014/4/20
Y1 - 2014/4/20
N2 - The gastrointestinal tract is composed of outer longitudinal muscle layers and inner circular muscle layers. Nitric oxide (NO), carbon monoxide (CO), and ATP play major roles as non-adrenergic non-cholinergic (NANC) inhibitory neurotransmitters in the longitudinal muscle of the mouse distal colon, whereas it is unclear which NANC inhibitory neurotransmitters are in its circular muscle. We investigated the electric field stimulation (EFS)-induced relaxations in the circular smooth muscle of the distal colon under NANC conditions. In the experiments in which Nω-nitro-L-arginine, an inhibitor of NO synthase, was added, the EFS-induced relaxation decreased in a concentration-dependent manner and finally vanished. In contrast, CO, purinergic receptor ligands, and peptidergic substances do not play major roles as NANC neurotransmitters in the circular muscle of the mouse distal colon. ODQ, an inhibitor of soluble guanylate cyclase, strongly attenuated EFS-induced relaxation. Ryanodine, a Ca2+ release modulator at the sarcoplasmic reticulum, strongly attenuated EFS-induced relaxation as well. Relaxation induced by NOR-1, which generates NO, was inhibited by ODQ and ryanodine. Next, we performed experiments that simultaneously measured tension and the cytoplasmic Ca2+ concentration ([Ca2+]cyt). NOR-1 decreased the tension and [Ca2+]cyt levels in the circular muscle. ODQ and ryanodine strongly attenuated the NOR-1-induced change in both tension and [Ca2+]cyt levels. In this study, we demonstrate that NO functions as a NANC inhibitory neurotransmitter in the circular muscle obtained from the mouse distal colon.
AB - The gastrointestinal tract is composed of outer longitudinal muscle layers and inner circular muscle layers. Nitric oxide (NO), carbon monoxide (CO), and ATP play major roles as non-adrenergic non-cholinergic (NANC) inhibitory neurotransmitters in the longitudinal muscle of the mouse distal colon, whereas it is unclear which NANC inhibitory neurotransmitters are in its circular muscle. We investigated the electric field stimulation (EFS)-induced relaxations in the circular smooth muscle of the distal colon under NANC conditions. In the experiments in which Nω-nitro-L-arginine, an inhibitor of NO synthase, was added, the EFS-induced relaxation decreased in a concentration-dependent manner and finally vanished. In contrast, CO, purinergic receptor ligands, and peptidergic substances do not play major roles as NANC neurotransmitters in the circular muscle of the mouse distal colon. ODQ, an inhibitor of soluble guanylate cyclase, strongly attenuated EFS-induced relaxation. Ryanodine, a Ca2+ release modulator at the sarcoplasmic reticulum, strongly attenuated EFS-induced relaxation as well. Relaxation induced by NOR-1, which generates NO, was inhibited by ODQ and ryanodine. Next, we performed experiments that simultaneously measured tension and the cytoplasmic Ca2+ concentration ([Ca2+]cyt). NOR-1 decreased the tension and [Ca2+]cyt levels in the circular muscle. ODQ and ryanodine strongly attenuated the NOR-1-induced change in both tension and [Ca2+]cyt levels. In this study, we demonstrate that NO functions as a NANC inhibitory neurotransmitter in the circular muscle obtained from the mouse distal colon.
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U2 - 10.1159/000363191
DO - 10.1159/000363191
M3 - Article
C2 - 25227243
AN - SCOPUS:84926309325
VL - 94
SP - 99
EP - 108
JO - Pharmacology
JF - Pharmacology
SN - 0031-7012
IS - 3-4
ER -