Adenylate cyclase and 5'-nucleotidase activities in rat liver plasma membranes were assayed in vitro in the presence of 4-hydroxy-2,3-trans-nonenal (HNE), a major end-product of microsomal lipid peroxidation. Both basal and glucagon-stimulated adenylate cyclase were inhibited in a dose-dependent manner, even at micromolar HNE concentrations, whereas fluoride-stimulated activity increased. A biphasic, dose- and time-dependent effect was noted when the basal activity was monitored at increasing doses. 5'-Nucleotidase activity was also decreased by HNE, but only at millimolar concentrations. These findings are related to the view that aldehydes, especially HNE, may act as diffusible cytotoxic compounds when lipid peroxidative derangement of membrane lipids is provoked by toxic conditions.
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