Effects of the catecholaminergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) on adrenal chromaffin cells in culture.
N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) is an inhibitor of noradrenaline uptake and a neurotoxin known to deplete noradrenaline levels with little effect on dopamine, serotonin or adrenaline in the central nervous system. The present study tested the effects of DSP-4 on catecholamine uptake, release and content in cultures of isolated bovine adrenal chromaffin cells. DSP-4 selectively inhibited the acute uptake of [3H]noradrenaline with little or no effect on [3H]adrenaline or [3H]dopamine uptake. In cultures preloaded with [3H]catecholamines, DSP-4 stimulated the release of [3H]noradrenaline and, to a small extent, also [3H]adrenaline and [3H]dopamine. However, the drug did not stimulate the release of appreciable amounts of endogenous adrenaline, noradrenaline or dopamine. A high concentration of DSP-4 inhibited the carbachol-stimulated release of adrenaline, noradrenaline and dopamine from the cells. Following a 1-hr exposure to the drug, DSP-4 decreased adrenaline, noradrenaline and dopamine levels in the cells with no gross morphologic changes in the cells. Reductions in adrenaline and noradrenaline levels were almost equal in magnitude, while dopamine was depleted to a somewhat greater extent under some conditions. Longer exposure to DSP-4 resulted in morphological changes in the cells, suggesting that the drug is also toxic to chromaffin cells in culture.
Boksa
P
P
Douglas Hospital Research Centre, Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Aitken
D
D
Meaney
M
M
D000818:Animals; D001596:Benzylamines / Q000633:toxicity*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002838:Chromaffin System / Q000187:drug effects*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D004837:Epinephrine / Q000032:analysis / Q000378:metabolism; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism
D001596:Benzylamines; D002395:Catecholamines; C012102:DSP 4; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine