Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle.

Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle. Research Abstract Details 

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Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle. Abstract Text:

Violeta N Mutafova-Yambolieva,Sung Jin Hwang,Xuemei Hao,Hui Chen,Michael X Zhu,Jackie D Wood,Sean M Ward,Kenton M Sanders,

Peripheral inhibitory nerves are physiological regulators of the contractile behavior of visceral smooth muscles. One of the transmitters responsible for inhibitory neurotransmission has been reputed to be a purine, possibly ATP. However, the exact identity of this substance has never been verified. Here we show that beta-nicotinamide adenine dinucleotide (beta-NAD), an inhibitory neurotransmitter candidate, is released by stimulation of enteric nerves in gastrointestinal muscles, and the pharmacological profile of beta-NAD mimics the endogenous neurotransmitter better than ATP. Levels of beta-NAD in superfusates of muscles after nerve stimulation exceed ATP by at least 30-fold; unlike ATP, the release of beta-NAD depends on the frequency of nerve stimulation. beta-NAD is released from enteric neurons, and release was blocked by tetrodotoxin or omega-conotoxin GVIA. beta-NAD is an agonist for P2Y1 receptors, as demonstrated by receptor-mediated responses in HEK293 cells expressing P2Y1 receptors. Exogenous beta-NAD mimics the effects of the enteric inhibitory neurotransmitter. Responses to beta-NAD and inhibitory junction potentials are blocked by the P2Y1-selective antagonist, MRS2179, and the nonselective P2 receptor antagonists, pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid and suramin. Responses to ATP are not blocked by these P2Y receptor inhibitors. The expression of CD38 in gastrointestinal muscles, and specifically in interstitial cells of Cajal, provides a means of transmitter disposal after stimulation. beta-NAD meets the traditional criteria for a neurotransmitter that contributes to enteric inhibitory regulation of visceral smooth muscles.

Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle. Publishing Authors By Initials

VN Mutafova-Yambolieva,SJ Hwang,X Hao,H Chen,MX Zhu,JD Wood,SM Ward,KM Sanders,

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Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 104

Page Numbers: 16359-64

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 3

MONTH: 10

YEAR: 2007

Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle. Information

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LANGUAGE: eng

NlmUniqueID: 7505876

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Grant and Affiliation Information for Beta-nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle.

AFFILIATION: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R21 NS056942

ACRONYM: NS

MEDLINETA: Proc Natl Acad Sci U S A

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