Presynaptic modulation of cholinergic and non-cholinergic fast synaptic transmission in the myenteric plexus of guinea pig ileum


James J. Galligan PhD, Department of Pharmacology and Toxicology, Life Science B440, Michigan State University, East Lansing, MI 48824, USA.
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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 μmol L−1) were cholinergic; mixed fEPSPs were inhibited <95% by hexamethonium. Non-cholinergic fEPSPs were studied in the presence of hexamethonium. The α2-adrenergic receptor agonist UK 14304 inhibited cholinergic (maximum inhibition = 76%, EC50 = 18 nmol L−1), mixed (81%, 21 nmol L−1) and non-cholinergic (76%, 44 nmol L−1) fEPSPs equally. The 5-HT1 receptor agonist 5-carboxamidotryptamine inhibited cholinergic, mixed and non-cholinergic fEPSPs equally. Renzapride, increased non-cholinergic (33%) less than mixed (97%, 13 μmol 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 μmol 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-HT4 receptor antagonist, SB 204070 (10 nmol L−1). Renzapride (0.3 μmol L−1) blocked 5-HT-induced increases in cholinergic fEPSPs. α2-Adrenergic and 5-HT1 receptors mediate inhibition of transmitter release from cholinergic and mixed terminals. 5-HT and prucalopride, acting at 5-HT4 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-HT4 receptors or a renzapride-insensitive 5-HT4 receptor isoform.