β-Nicotinamide adenine dinucleotide is an inhibitory neurotransmitter in visceral smooth muscle

• DOI: 10.1073/pnas.0705510104
• Publication Date: 2007-10-04T00:53:32Z
• Authors: Violeta N. Mutafo...; Sung Jin Hwang; Xuemei Hao; Hui Chen; Michael X. Zhu; Jackie D. Wood; Sean M. Ward; Kenton M. Sanders
• Keywords: PPADS; P2Y receptor; Purinergic Signalling

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