The muscarinic receptor agonist oxotremorine methiodide evokes a nicotinic response in mammalian sympathetic neurons

Oxotremorine methiodide, a congener of oxotremorine, is used as a muscarinic receptor agonist. Responses to oxotremorine methiodide and nicotinic receptor agonists were examined in cultured guinea-pig celiac neurons using whole-cell voltage clamp techniques. At holding potentials between -30 and -60 mV, a brief application of oxotremorine methiodide produced fast and slow inward current transients, depending upon the concentration applied. Slowly developing inward current transients, characteristic of muscarinic responses, were produced by lower concentrations (EC₅₀: 0.3 μM) and were blocked by atropine. Rapid inward current transients, characteristic of nicotine responses, were produced by higher concentrations of oxotremorine methiodide (EC₅₀: 168 μM) and were blocked by d-tubocurarine. Thus oxotremorine methiodide, at concentrations of 10 μM and greater, produced an initial nicotinic fast inward current transient followed by a slow muscarinic inward transient. The fast inward transients were similar to responses evoked by the nicotinic receptor agonists acetylcholine, nicotine and 1,1-dimethyl-4-phenyl-piperazinium iodide and were not antagonized by atropine. We conclude that oxotremorine methiodide acts as a nicotinic and muscarinic receptor agonist in celiac sympathetic ganglion neurons.