Activation of the frog sartorius acetylcholine receptor by a covalently attached group.
The frog sartorius motor endplate was treated with the specific disulfide bond reducing agent dithiothreitol and subsequently exposed to a covalently reacting compound (the nitrophenyl ester of p-carboxyphenyltrimethylammonium iodide, NPTMB) known to activate the dithiothreitol-reduced acetylcholine receptor in Electrophorus electroplax. NPTMB causes a maximum depolarization of about 35 mV when applied to the dithiothreitol-treated sartorious motor endplate. It is ineffective on postjunctional membrane prior to disulfide bond reduction and on extrajunctional regions, reduced or unreduced. High concentrations of a competitive antagonist such as (+)-tubocurarine prevent reaction between NPTMB and the reduced receptor and cause a repolarization of the membrane when applied to the already-depolarized preparation. We conclude that in frog muscle, as in electroplax, the attached activator bridges the acetylcholine binding site of the reduced receptor between a sulfhydryl group, to which it is covalently bound, and a negative subsite, with which it forms a reversible ionic band.
D000109:Acetylcholine; D000818:Animals; D001001:Anura; D008725:Bis-Trimethylammonium Compounds / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology*; D009132:Muscles / Q000294:innervation*; D009467:Neuromuscular Depolarizing Agents; D009469:Neuromuscular Junction / Q000502:physiology*; D010084:Oxidation-Reduction; D011894:Rana pipiens; D011950:Receptors, Cholinergic / Q000378:metabolism*; D014403:Tubocurarine / Q000494:pharmacology
D008725:Bis-Trimethylammonium Compounds; D009467:Neuromuscular Depolarizing Agents; D011950:Receptors, Cholinergic; D000109:Acetylcholine; D004229:Dithiothreitol; D014403:Tubocurarine