Extraneuronal effects of 6-hydroxydopamine

Summary The effects of various concentrations of 6-hydroxydopamine (6OHDA) on rat adrenocortical cells in tissue culture were studied with phase contrast and electron microscopy. With 40 mg/l of 6-OHDA the first signs of alteration as revealed by microcinematography appeared in isolated cortical cells as early as 15 min after addition of the drug. There was a cessation of movement of cell organelles and an immobilisation of membrane undulations followed by the development of dark inclusion bodies. The cells underwent increasing shrinkage and collapsed by 11/2 h. Chromaffin cells were not affected until 45 min after exposure to the drug and neurons were the most resistant population. However 61/2 h after application of the drug most cells in the culture were dead. 6-OHDA applied in different doses and to adrenal expiants did not alter the sequence of events. Ultrastructurally cortex cells underwent damage along two lines: they either showed lytic changes or developed various types of dense bodies before reaching the lytic stage.Treatment of cortical cells with 40 mg/l 5-or 6-OHDA followed by exposure to buffered 2% glyoxylic acid and heat did not produce a fluorescence within the cells. Microspectrofluorimetry on amine models with noradrenaline, 5- and 6-OHDA revealed that neither 5-nor 6-OHDA are capable to form a fluorophore with glyoxylic acid.Dedicated to Professor Berta Scharrer in honor of her 70th birthdaySupported by a grant from Deutsche Forschungsgemeinschaft (Un 34/3) and a Research Fellowship of the University of Melbourne to K.U., and a Research Fellowship and Grant-in-Aid from the Life Insurance Medical Research Fund of Australia and New Zealand to J.H.C.