title: Inactivation by 6-hydroxydopamine of the cerebral factor(s) responsible for the inhibition of the autoxidation of norepinephrine in vitro.
abstract: The effect of extracts from rat cerebral cortex was examined on the stability of norepinephrine-HC1 (NE) in 16 mM Na-phosphate buffer, pH 7.4, at 37 degrees C. The autoxidation products of NE were detected spectrophotometrically at 480 nm. Dialysed samples from a synaptosomal preparation and from the 100,000 g supernatant of a crude homogenate were tested. Aliquots from these preparations, in the range of 0.005-5.0 or 0.01-10.0 micrograms protein/ml, respectively, produced up to 80-85% inhibition of the autoxidation of 100 microM NE for a period of at least 3 h. Similar results were obtained with albumin and ovalbumin at 10- and 10(3)-times higher concentrations, respectively. After the preparations were exposed to 0.1-1.0 mg 6-hydroxydopamine-HC1/mg protein for 5 min at 25 degrees C followed by rapid dialysis, the maximal inhibitory effect was reduced to between 95% to less than 5% of control values. The percent inactivation by a given quantity of 6-hydroxydopamine (6-OHDA) was inversely related to the potency of the untreated sample. Additional observations are presented which suggest that the destruction of the antioxidant activity is caused by breakdown products of 6-OHDA reacting with nucleophilic sites of the preparation. Similar inactivating substances are expected to be formed from other autoxidizing catecholamines, although at a slower rate.
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006892:Hydroxydopamines / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D006892:Hydroxydopamines; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D009638:Norepinephrine