HALOTHANE AND ISOFLURANE DOSE-DEPENDENTLY INHIBIT THE CYCLIC-GMP INCREASE CAUSED BY N-METHYL-D-ASPARTATE IN RAT CEREBELLUM - NOVEL LOCALIZATION AND QUANTITATION BY IN-VITRO AUTORADIOGRAPHY

Using a novel technique combining immunohistochemistry and in vitro qu antitative autoradiography, we were able simultaneously to localize an d quantitate cyclic guanosine 3',5'-monophosphate (cGMP)-immunoreactiv e binding in adult rat cerebellum. The cGMP-immunoreactive binding was predominantly detected in the molecular layer of the cerebellum under both basal and N-methyl-D-aspartate-stimulated conditions. N-Methyl-D -aspartate significantly increased the cGMP binding density in the mol ecular layer. This increased cGMP level was dose-dependently and signi ficantly inhibited by the inhalational anesthetics halothane and isofl urane. This increased cGMP level was also significantly inhibited by L -N-G-nitroarginine methyl ester, an inhibitor of nitric oxide synthase s. L-Arginine, the substrate of nitric oxide synthase, reversed the in hibition by L-N-G-nitroarginine methyl ester on the cGMP increase. Thi s novel combination of immunohistochemistry and quantitative autoradio graphy may be used to localize and quantitate simultaneously cGMP or o ther substances in animal tissues. Our data also confirm that nitric o xide is involved in the stimulation of cGMP formation by N-methyl-D-as partate. Halothane and isoflurane inhibit the nitric oxide-guanylyl cy clase signaling pathway activated by the excitatory amino acid N-methy l-D-aspartate in the brain, which may be a component of the mechanisms by which these two inhalational anesthetics produce their anesthetic effects. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.