期刊
NEUROGASTROENTEROLOGY AND MOTILITY
卷 25, 期 3, 页码 E194-E204出版社
WILEY
DOI: 10.1111/nmo.12069
关键词
ATP; enteric nervous system; myenteric ganglia; nicotinamide adenine dinucleotide; nicotinic acetylcholine receptors; purines; 5-HT3 receptors
资金
- NIH [PO1 DK41315]
Background The purinergic component of enteric inhibitory neurotransmission is important for normal motility in the gastrointestinal (GI) tract. Controversies exist about the purine(s) responsible for inhibitory responses in GI muscles: ATP has been assumed to be the purinergic neurotransmitter released from enteric inhibitory motor neurons; however, recent studies demonstrate that beta-nicotinamide adenine dinucleotide (beta-NAD(+)) and ADP-ribose mimic the inhibitory neurotransmitter better than ATP in primate and murine colons. The study was designed to clarify the sources of purines in colons of Cynomolgus monkeys and C57BL/6 mice. Methods High-performance liquid chromatography with fluorescence detection was used to analyze purines released by stimulation of nicotinic acetylcholine receptors (nAChR) and serotonergic 5-HT3 receptors (5-HT3R), known to be present on cell bodies and dendrites of neurons within the myenteric plexus. Key Results Nicotinic acetylcholine receptor or 5-HT3R agonists increased overflow of ATP and beta-NAD(+) from tunica muscularis of monkey and murine colon. The agonists did not release purines from circular muscles of monkey colon lacking myenteric ganglia. Agonist-evoked overflow of beta-NAD(+), but not ATP, was inhibited by tetrodotoxin (0.5 mu mol L-1) or omega-conotoxin GVIA (50 nmol L-1), suggesting that beta-NAD(+) release requires nerve action potentials and junctional mechanisms known to be critical for neurotransmission. ATP was likely released from nerve cell bodies in myenteric ganglia and not from nerve terminals of motor neurons. Conclusions & Inferences These results support the conclusion that ATP is not a motor neurotransmitter in the colon and are consistent with the hypothesis that beta-NAD(+), or its metabolites, serve as the purinergic inhibitory neurotransmitter.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据