CARNOSINE AND OTHER IMIDAZOLE-CONTAINING COMPOUNDS ENHANCE THE POSTDENERVATION DEPOLARIZATION OF THE RAT DIAPHRAGM FIBERS

In the presence of carnosine, anserine, histidine, imidazole and 7-nit ro indazole, the early postdenervation depolarization of muscle of abo ut 8 mV was significantly increased by 2.15-4.8 mV. The presence of th e imidazole ring in the molecule is apparently necessary for this effe ct. These compounds also eliminated an NO-mediated protective effect o f L-glutamate and carbachol on the depolarization of membrane potentia l. The presence of imidazole, 7-nitro indazole, carnosine and anserine did not significantly change the effect of an external NO donor, sodi um nitroprusside. The structural and functional similarity between imi dazole derivatives and the known NO synthase inhibitor, 7-nitro indazo le suggests that imidazole, carnosine and anserine might act by inhibi ting NO production which is stimulated by glutamate and carbachol.