Electrical stimulation of the mucosa evokes slow EPSPs mediated by NK1 tachykinin receptors and by P2Y1 purinoceptors in different myenteric neurons.
Slow excitatory postsynaptic potentials (EPSPs) in enteric neurons arise from diverse sources, but which neurotransmitters mediate specific types of slow EPSPs is unclear. We investigated transmitters and receptors mediating slow EPSPs in myenteric neurons evoked by electrical stimulation of the mucosa in guinea pig small intestine. Segments of ileum or jejunum were dissected to allow access to the myenteric plexus adjacent to intact mucosa, in vitro. AH and S neurons were impaled with conventional intracellular electrodes. Trains of stimuli delivered to the mucosa evoked slow EPSPs in AH neurons that were blocked or depressed by the neurokinin-1 (NK1) tachykinin antagonist SR140333 (100 nM) in 10 of 11 neurons; the NK3 tachykinin receptor antagonist SR142801 (100 nM) had no effect on slow EPSPs in seven of nine AH neurons. Single pulses to the mucosa evoked fast EPSPs and slow depolarizations in S neurons. The depolarizations were divided into intermediate (durations 300-900 ms) or slow (durations 1.3-9 s) EPSPs. The slow EPSPs were blocked by pyridoxal phosphate-6-axophenyl-2-4-disulfonic acid (30 microM, N = 3) or the specific P2Y(1) antagonist MRS 2179 (10 microM, N = 6) and were predominantly in anally projecting S neurons that were immunoreactive for nitric oxide synthase (NOS). In contrast, intermediate EPSPs were predominantly evoked in NOS-negative neurons; these were abolished by MRS 2179 (N = 8). Thus activation of pathways running from the mucosa excites three different types of slow EPSP in myenteric neurons, which are mediated by either a tachykinin (NK1, AH neurons) or a purine nucleotide (P2Y(1), S neurons).
Gwynne
Rachel M
RM
Department of Physiology, University of Melbourne, Parkville, Victoria 3010, Australia. rgwynne@unimelb.edu.au
Bornstein
Joel C
JC
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000294:innervation*; D007583:Jejunum / Q000294:innervation*; D007700:Kinetics; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D064729:Neurokinin-1 Receptor Antagonists; D026602:Nitrergic Neurons / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058472:Receptors, Purinergic P2Y1
C111914:N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D058919:Purinergic P2 Receptor Antagonists; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C085215:SR 140333; D011732:Pyridoxal Phosphate; D000244:Adenosine Diphosphate; D052248:Nitric Oxide Synthase Type I; C091554:SR 142801