Presynaptic modulation of cholinergic and non-cholinergic fast synaptic transmission in the myenteric plexus of guinea pig ileum.
Abstract These studies investigated receptors modulating release of mediators of fast excitatory postsynaptic potentials (fEPSPs) in guinea pig ileum myenteric plexus using electrophysiological methods. Fast EPSPs inhibited by >95% by hexamethonium (100 micromol L(-1)) were cholinergic; mixed fEPSPs were inhibited <95% by hexamethonium. Non-cholinergic fEPSPs were studied in the presence of hexamethonium. The alpha2-adrenergic receptor agonist UK 14304 inhibited cholinergic (maximum inhibition = 76%, EC(50) = 18 nmol L(-1)), mixed (81%, 21 nmol L(-1)) and non-cholinergic (76%, 44 nmol L(-1)) fEPSPs equally. The 5-HT(1) receptor agonist 5-carboxamidotryptamine inhibited cholinergic, mixed and non-cholinergic fEPSPs equally. Renzapride, increased non-cholinergic (33%) less than mixed (97%, 13 micromol L(-1)) fEPSPs. Renzapride inhibited the purely cholinergic fEPSPs (-29%) but potentiated the cholinergic component of mixed fEPSPs (39%). Prucalopride potentiated all fEPSPs equally (30-33%). 5-HT (0.1 micromol L(-1)) induced potentiation of cholinergic (75%), mixed (97%) and non-cholinergic (84%) fEPSPs was not statistically different. The potentiating effects of renzapride and 5-HT on fEPSPs were inhibited by the 5-HT(4) receptor antagonist, SB 204070 (10 nmol L(-1)). Renzapride (0.3 micromol L(-1)) blocked 5-HT-induced increases in cholinergic fEPSPs. alpha2-Adrenergic and 5-HT(1) receptors mediate inhibition of transmitter release from cholinergic and mixed terminals. 5-HT and prucalopride, acting at 5-HT(4) receptors, facilitate all fEPSPs; renzapride facilitates the cholinergic and non-cholinergic components of mixed fEPSPs but not purely cholinergic fEPSPs. Cholinergic synapses may express few 5-HT(4) receptors or a renzapride-insensitive 5-HT(4) receptor isoform.
LePard
K J
KJ
Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State, University, East Lansing, MI 48824, USA.
Ren
J
J
Galligan
J J
JJ
D000109:Acetylcholine / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation*; D009197:Myenteric Plexus / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D000109:Acetylcholine