title: β-Nicotinamide adenine dinucleotide acts at prejunctional adenosine A1 receptors to suppress inhibitory musculomotor neurotransmission in guinea pig colon and human jejunum.
abstract: Intracellular microelectrodes were used to record neurogenic inhibitory junction potentials in the intestinal circular muscle coat. Electrical field stimulation was used to stimulate intramural neurons and evoke contraction of the smooth musculature. Exposure to β-nicotinamide adenine dinucleotide (β-NAD) did not alter smooth muscle membrane potential in guinea pig colon or human jejunum. ATP, ADP, β-NAD, and adenosine, as well as the purinergic P2Y1 receptor antagonists MRS 2179 and MRS 2500 and the adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine, each suppressed inhibitory junction potentials in guinea pig and human preparations. β-NAD suppressed contractile force of twitch-like contractions evoked by electrical field stimulation in guinea pig and human preparations. P2Y1 receptor antagonists did not reverse this action. Stimulation of adenosine A1 receptors with 2-chloro-N6-cyclopentyladenosine suppressed the force of twitch contractions evoked by electrical field stimulation in like manner to the action of β-NAD. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine suppressed the inhibitory action of β-NAD on the force of electrically evoked contractions. The results do not support an inhibitory neurotransmitter role for β-NAD at intestinal neuromuscular junctions. The data suggest that β-NAD is a ligand for the adenosine A1 receptor subtype expressed by neurons in the enteric nervous system. The influence of β-NAD on intestinal motility emerges from adenosine A1 receptor-mediated suppression of neurotransmitter release at inhibitory neuromuscular junctions.
authors: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors: Guo-Du
authors: GD
authors: Wang
authors: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors: Xi-Yu
authors: XY
authors: Wang
authors: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors: Sumei
authors: S
authors: Liu
authors: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio; Department of Anesthesiology, College of Medicine, The Ohio State University, Columbus, Ohio; and.
authors: Yun
authors: Y
authors: Xia
authors: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors: Fei
authors: F
authors: Zou
authors: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors: Meihua
authors: M
authors: Qu
authors: Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio.
authors: Bradley J
authors: BJ
authors: Needleman
authors: Department of Surgery, College of Medicine, The Ohio State University, Columbus, Ohio.
authors: Dean J
authors: DJ
authors: Mikami
authors: Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
authors: Jackie D
authors: JD
authors: Wood
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D058907:Adenosine A1 Receptor Agonists / Q000493:pharmacokinetics; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000818:Animals; D003106:Colon / Q000473:pathology / Q000502:physiology*; D003838:Deoxyadenine Nucleotides / Q000493:pharmacokinetics; D004558:Electric Stimulation / Q000379:methods; D006168:Guinea Pigs; D006801:Humans; D007583:Jejunum / Q000473:pathology / Q000502:physiology*; D008024:Ligands; D008564:Membrane Potentials / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000502:physiology; D009243:NAD / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000502:physiology; D058921:Purinergic P2Y Receptor Antagonists / Q000493:pharmacokinetics; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: C495475:2-iodo-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine-3',5'-bisphosphate; D058907:Adenosine A1 Receptor Agonists; D003838:Deoxyadenine Nucleotides; D008024:Ligands; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D058921:Purinergic P2Y Receptor Antagonists; D043682:Receptor, Adenosine A1; D009243:NAD; C058394:2-chloro-N(6)cyclopentyladenosine; D000244:Adenosine Diphosphate; D000241:Adenosine
keywords: enteric neuromuscular transmission; intestinal motility; purinergic receptors; smooth muscle