Evidence that nitric oxide is a non-adrenergic non-cholinergic inhibitory neurotransmitter in the circular muscle of the mouse distal colon: A study on the mechanism of nitric oxide-induced relaxation

Kazuhiro Nishiyama, Yasu Taka Azuma, Kazuma Shintaku, Natsuho Yoshida, Hidemitsu Nakajima, Tadayoshi Takeuchi

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)99-108
Number of pages10
JournalPharmacology
Volume94
Issue number3-4
DOIs
Publication statusPublished - Apr 20 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

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