Is an endothelin a neurotoxic factor in the brain?

A possible role for endothelin in the pathogenesis of hypoglycemic brain damage in rats was evaluated using an in vitro model with which we could directly monitor the release of dopamine from striatal slices. There was no evidence of impairment in case of non-exposure of the slices to endothelin-3 during 20-40 min of hypoglycemia. The response all but disappeared in striatal slices stimulated twice with 10(?5) M endothelin-3 during 20 min of hypoglycemia. Hypoglycemic damage triggered by endothelin-3 was not observed in the absence of extracellular Ca(2+). Nifedipine (10(?6) M), but not verapamil (10(?5) M) nor diltiazem (10(?5)M), protected striatal tissue from this damage. Our findings provide evidence that endothelins might be etiological factors in the development of hypoglycemic/ischemic brain injury by stimulating dihydropyridine-regulated Ca(2+) influx.