Effects of metalloendoproteinase inhibitors on secretion and intracellular free calcium in bovine adrenal chromaffin cells.

The possible role of metalloendoproteinase in stimulus-secretion coupling in adrenal chromaffin cells was examined using the metalloendoproteinase inhibitors 1,10-phenanthroline and carbobenzoxy-Gly-Phe-NH2. Catecholamine release elicited by nicotine or by depolarisation with 55 mM K+ was almost completely abolished by 0.5 mM 1,10-phenanthroline. Carbobenzoxy-Gly-Phe-NH2 (2.5 mM) inhibited catecholamine release in response to nicotine but enhanced that due to 55 mM K+. The rise in intracellular free calcium, [Ca2+]i, in response to either nicotine or 55 mM was inhibited by about 50% by both inhibitors. One site of action of metalloendoproteinase inhibitors may, therefore, be at the level of the regulation of [Ca2+]i. Catecholamine release and the rise in [Ca2+]i elicited by the calcium ionophore ionomycin were not reduced by the inhibitors. These results show that metalloendoproteinase inhibitors have complex effects on chromaffin cells including effects on the regulation of [Ca2+]i but do not inhibit calcium-activated exocytosis itself.