THE MUSCARINIC RECEPTOR AGONIST OXOTREMORINE METHIODIDE EVOKES A NICOTINIC RESPONSE IN MAMMALIAN SYMPATHETIC NEURONS

Oxotremorine methiodide, a congener of oxotremorine, is used as a musc arinic receptor agonist. Responses to oxotremorine methiodide and nico tinic receptor agonists were examined in cultured guinea-pig celiac ga nglion neurons using whole-cell voltage clamp techniques. At holding p otentials 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 tran sients, characteristic of muscarinic responses, were produced by lower concentrations (EC(50): 0.3 mu M) and were blocked by atropine. Rapid inward current transients, characteristic of nicotinic responses, wer e produced by higher concentrations of oxotremorine methiodide (EC(50) : 168 mu M) and were blocked by d-tubocurarine. Thus oxotremorine meth iodide, at concentrations of 10 mu M 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 nicotini c and muscarinic receptor agonist in celiac sympathetic ganglion neuro ns.