Biphasic effects of chromium compounds on catecholamine secretion from bovine adrenal medullary cells.

CrO3 was found to affect norepinephrine release in a biphasic manner: at concentrations above 100 microM, it inhibited, while at concentrations below 10 microM, it enhanced DMPP- and high K+-induced [3H]norepinephrine (NE) release from bovine adrenal medullary cells. Similar effects were found for K2Cr2O7. CrO3 inhibited the 45Ca2+ uptake induced by DMPP and high K+, suggesting that the voltage-gated Ca2+ channels are possible sites of the inhibitory action of CrO3. CrCl3, possessing a trivalent state in contrast to the hexavalent states of CrO3, K2Cr2O7, inhibited DMPP-induced [3H] release and inhibited, to a lesser extent, high K+-induced [3H]-NE release, suggesting that nicotinic receptors are also possible sites of Cr3+ action. In medullary cells permeabilized with digitonin, both CrO3 and CrCl3 induced [3H]-NE release from cells preloaded with [3H]-NE. In intact cells, CrO3 but not CrCl3 enhanced secretagogue-induced [3H]-NE release and entered into the cells as demonstrated by fluorescence quenching experiments. These results suggest that chromium compounds can induce catecholamine secretion after entering the cytoplasm. The enhancement of norepinephrine release induced by chromium ions appears to be due to interference with the intracellular functions of Ca2+ in the cytoplasm.