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.
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002837:Chromaffin Granules / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism*; D010450:Endopeptidases / Q000502:physiology; D004987:Ethers / Q000494:pharmacology; D066298:In Vitro Techniques; D015759:Ionomycin; D008666:Metalloendopeptidases; D009538:Nicotine / Q000494:pharmacology; D010618:Phenanthrolines / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011480:Protease Inhibitors
D002395:Catecholamines; D004987:Ethers; D010618:Phenanthrolines; D011480:Protease Inhibitors; C017105:carbobenzoxyphenylalanine; D010649:Phenylalanine; D015759:Ionomycin; D009538:Nicotine; D010450:Endopeptidases; D008666:Metalloendopeptidases; D011188:Potassium; D002118:Calcium; C025205:1,10-phenanthroline