[125I]endothelin binding in rat cerebellum is increased following L-2-chloropropionic-acid-induced granule cell necrosis.
The systemic administration of L-2-chloropropionic acid (L-CPA) to rats produced a marked depletion of cerebellar granule cells (> 80% of the total) when administered in a single oral dose of 750 or 250 mg/kg/day for 3 days. The nature of the L-CPA-induced neurotoxicity is currently unknown but it exhibits a number of features in common with excitatory amino acid-induced neuronal cell death. We observed an increase in [125I]endothelin-1 (ET-1) binding in the cerebellar cortex, as measured by quantitative receptor autoradiography, which occurs at 48 h, but not 24 h, following the 750 mg/kg L-CPA dosing regimen. The increase in [125I]ET-1 binding did not parallel the cellular damage and resultant astrocyte proliferation, as measured by GFAP immunoreactivity, which was primarily confined to the granular layer of the cerebellar cortex. The increased [125I]ET-1 binding occurred in the molecular layer of the cerebellar cortex (controls 2.03 +/- 0.26 fmol/mg tissue; L-CPA-treated 6.69 +/- 0.45 fmol/mg tissue, n = 6; p < 0.01, Student's t-test) which appeared to contain astrocytic processes originating from the large increase in astrocyte number situated in the granular layer. Pretreatment of the rats with the irreversible NMDA receptor antagonist, MK-801, protected the cerebellar granule cells against the L-CPA neurotoxicity and also prevented the increase in [125I]ET-1 binding in the cerebellar cortex. The increased [125I]ET-1 binding in rat cerebellum appears to be linked to the reactive gliosis that occurs in association with neuronal cell injury.
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016232:Endothelins / Q000378:metabolism*; D006843:Hydrocarbons, Chlorinated; D007457:Iodine Radioisotopes; D008297:Male; D009336:Necrosis; D009498:Neurotoxins / Q000633:toxicity*; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D017466:Receptors, Endothelin / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013997:Time Factors
D016232:Endothelins; D006843:Hydrocarbons, Chlorinated; D007457:Iodine Radioisotopes; D009498:Neurotoxins; D011422:Propionates; D017466:Receptors, Endothelin; C021974:2-chloropropionic acid