Catecholamine toxicity in cerebral cortex in dissociated cell culture.
Identification of endogenous toxins and characterization of the mechanisms by which toxins produce cell injury and death may help understand both normal modeling of cell populations and connections in the CNS as well as abnormal cell loss. The toxicity of catecholamines intrinsic to the CNS was investigated using the model system of rat cerebral cortex in dissociated cell culture. All catecholamines tested, including norepinephrine (NE), dopamine, and epinephrine, were toxic to neurons as well as glia at a concentration of 25 microM when added to cultures 24 hr after plating. Toxicity was evident after 48 hr exposure to NE, as monitored by loss of cells from the cultures. Toxicity did not seem to be mediated by adrenergic receptors because, although the beta-adrenergic agonist isoproterenol (but not the alpha-adrenergic agonist phenylephrine) was similar in its toxic effect to NE, the beta-adrenergic antagonist atenolol did not block the toxic effect of NE. Toxicity could be mimicked by hydrogen peroxide, a product of the oxidative degradation of catecholamines. Toxicity of NE was blocked by catalase. The neurotoxin 6-hydroxydopamine (6-OHDA), supposedly selective for catecholaminergic neurons, was found to be toxic over the same concentration range as NE. These results suggest that endogenous catecholamines may play a role in normal and abnormal cell death, and suggest that caution be used in relying on the specificity of 6-OHDA and other supposedly selective neurotoxins.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena; D002374:Catalase / Q000494:pharmacology; D002395:Catecholamines / Q000506:poisoning*; D002452:Cell Count / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology; D009994:Osmolar Concentration; D011941:Receptors, Adrenergic / Q000502:physiology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D009498:Neurotoxins; D011941:Receptors, Adrenergic; D002374:Catalase