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

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

Proceedings of the National Academy of Sciences of the United States of America (2007-10-05)
Violeta N Mutafova-Yambolieva, Sung Jin Hwang, Xuemei Hao, Hui Chen, Michael X Zhu, Jackie D Wood, Sean M Ward, Kenton M Sanders
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
β-Nicotinamide adenine dinucleotide hydrate, ≥95% (HPLC)
Sigma-Aldrich
β-Nicotinamide adenine dinucleotide, pkg of 10 mg (per vial)