title: Transmission to interneurons is via slow excitatory synaptic potentials mediated by P2Y(1) receptors during descending inhibition in guinea-pig ileum.
abstract: BACKGROUND
  The nature of synaptic transmission at functionally distinct synapses in intestinal reflex pathways has not been fully identified. In this study, we investigated whether transmission between interneurons in the descending inhibitory pathway is mediated by a purine acting at P2Y receptors to produce slow excitatory synaptic potentials (EPSPs).
  
  
  RESULTS
  Myenteric neurons from guinea-pig ileum in vitro were impaled with intracellular microelectrodes. Responses to distension 15 mm oral to the recording site, in a separately perfused stimulation chamber and to electrical stimulation of local nerve trunks were recorded. A subset of neurons, previously identified as nitric oxide synthase immunoreactive descending interneurons, responded to both stimuli with slow EPSPs that were reversibly abolished by a high concentration of PPADS (30 μM, P2 receptor antagonist). When added to the central chamber of a three chambered organ bath, PPADS concentration-dependently depressed transmission through that chamber of descending inhibitory reflexes, measured as inhibitory junction potentials in the circular muscle of the anal chamber. Reflexes evoked by distension in the central chamber were unaffected. A similar depression of transmission was seen when the specific P2Y(1) receptor antagonist MRS 2179 (10 μM) was in the central chamber. Blocking either nicotinic receptors (hexamethonium 200 μM) or 5-HT(3) receptors (granisetron 1 μM) together with P2 receptors had no greater effect than blocking P2 receptors alone.
  
  
  CONCLUSIONS
  Slow EPSPs mediated by P2Y(1) receptors, play a primary role in transmission between descending interneurons of the inhibitory reflexes in the guinea-pig ileum. This is the first demonstration for a primary role of excitatory metabotropic receptors in physiological transmission at a functionally identified synapse.
authors: Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
authors: Peter D J
authors: PD
authors: Thornton
authors: Rachel M
authors: RM
authors: Gwynne
authors: Darren J
authors: DJ
authors: McMillan
authors: Joel C
authors: JC
authors: Bornstein
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1 / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D018733:Nicotinic Antagonists; D058921:Purinergic P2Y Receptor Antagonists; D011978:Receptors, Nicotinic; D058472:Receptors, Purinergic P2Y1; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000244:Adenosine Diphosphate
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