title: P2Y(1)  knockout mice lack purinergic neuromuscular transmission in the antrum and cecum.
abstract: BACKGROUND
  Pharmacological studies using selective P2Y(1) antagonists, such as MRS2500, and studies with P2Y(1)(-/-) knockout mice have demonstrated that purinergic neuromuscular transmission is mediated by P2Y(1) receptors in the colon. The aim of the present study was to test whether P2Y(1) receptors are involved in purinergic neurotransmission in the antrum and cecum.
  
  
  METHODS
  Microelectrode recordings were performed on strips from the antrum and cecum of wild type animals (WT) and P2Y(1)(-/-) mice.
  
  
  RESULTS
  In the antrum, no differences in resting membrane potential and slow wave activity were observed between groups. In WT animals, electrical field stimulation elicited a MRS2500-sensitive inhibitory junction potential (IJP). In P2Y(1)(-/-) mice, a nitrergic IJP (N(ω) -nitro-l-arginine-sensitive), but not a purinergic IJP was recorded. This IJP was equivalent to the response obtained in strips from WT animals previously incubated with MRS2500. Similar results were obtained in the cecum: 1- the purinergic IJP (MRS2500-sensitive) recorded in WT animals was absent in P2Y(1)(-/-) mice 2- nitrergic neurotransmission was preserved in both groups. Moreover, 1- spontaneous IJP (MRS2500-sensitive) could be recorded in WT, but not in P2Y(1)(-/-) mice 2- MRS2365 a P2Y(1) agonist caused smooth muscle hyperpolarization in WT, but not in P2Y(1) (-/-) animals, and 3- β-NAD caused smooth muscle hyperpolarization both in WT and P2Y(1)(-/-) animals.
  
  
  CONCLUSIONS
  1- P2Y(1) receptor is the general mechanism of purinergic inhibition in the gastrointestinal tract, 2- P2Y(1)(-/-) mouse is a useful animal model to study selective impairment of purinergic neurotransmission and 3- P2Y(1)(-/-) mouse might help in the identification of purinergic neurotransmitter(s).
authors: Department of Cell Biology, Physiology and Immunology and Neuroscience Institute, Universitat Autònoma de Barcelona, Bellaterra, Spain.
authors: V
authors: V
authors: Gil
authors: M
authors: M
authors: Martínez-Cutillas
authors: N
authors: N
authors: Mañé
authors: M T
authors: MT
authors: Martín
authors: M
authors: M
authors: Jiménez
authors: D
authors: D
authors: Gallego
mesh_terms: D000818:Animals; D002432:Cecum / Q000502:physiology*; D004594:Electrophysiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008839:Microelectrodes; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D058919:Purinergic P2 Receptor Antagonists / Q000494:pharmacology; D011706:Pyloric Antrum / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D058919:Purinergic P2 Receptor Antagonists; D058472:Receptors, Purinergic P2Y1