title: Nitrergic and purinergic mechanisms evoke inhibitory neuromuscular transmission in the human small intestine.
abstract: BACKGROUND
  Inhibitory neuromuscular transmission in the human colon is due to nitrergic and purinergic (P2Y1 -mediated) inputs. The aim of this study was to determine the mechanisms of neuromuscular transmission in different regions of the human small intestine.
  
  
  METHODS
  Ileal (n = 6) and jejunal (n = 6) samples underwent histological examination and were studied using sharp microelectrodes in smooth muscle cells and conventional muscle bath techniques. Electrical field stimulation (EFS) was used to stimulate inhibitory neurons.
  
  
  RESULTS
  No histological abnormalities were found. Resting membrane potential was -39.7 ± 1.5 and -45.5 ± 2.1 mV in the jejunum and ileum, respectively. Slow waves and spontaneous contractions were recorded at a frequency of about 8-9 and 6-7 cpm in the jejunum and ileum, respectively. In non-adrenergic, non-cholinergic conditions, EFS caused an inhibitory junction potential and mechanical relaxation. Both responses were blocked by tissue incubation with the nitric oxide synthase inhibitor (Nω-nitro-l-arginine 1 mM) and the P2Y1 receptor blocker 2'-deoxy-N(6) -methyladenosine 3',5'-bisphosphate tetrasodium salt (MRS2179; 10 μM). Both exogenous addition of sodium nitroprusside (1 μM) and the preferential P2Y1 receptor agonist ADPβS (1 μM) hyperpolarized and relaxed smooth muscle cells. MRS2179 (10 μM) blocked ADPβS-induced responses.
  
  
  CONCLUSIONS
  Similar to colon, inhibitory neurotransmission in the human small intestine is mainly mediated by purinergic (via P2Y1 receptors) and nitrergic inhibitory neurotransmission. Similar mechanisms of inhibitory neurotransmission are present in different regions of the human intestine.
authors.affiliation: Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain; Department of Cell Biology, Physiology and Immunology and Neurosciences Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Gallego
authors.forename: C
authors.initials: C
authors.lastname: Malagelada
authors.forename: A
authors.initials: A
authors.lastname: Accarino
authors.forename: R
authors.initials: R
authors.lastname: De Giorgio
authors.forename: J R
authors.initials: JR
authors.lastname: Malagelada
authors.forename: F
authors.initials: F
authors.lastname: Azpiroz
authors.forename: M
authors.initials: M
authors.lastname: Jimenez
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000368:Aged; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D007583:Jejunum / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D020030:Nitric Oxide Donors; D058921:Purinergic P2Y Receptor Antagonists; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; D009599:Nitroprusside; D019335:Nitroarginine; C030812:adenosine 5'-O-(2-thiodiphosphate); D000244:Adenosine Diphosphate
keywords: IJP; P2Y1 receptors; ileum; jejunum; purinergic