Naphthalenesulfonamide derivatives ML9 and W7 inhibit catecholamine secretion in intact and permeabilized chromaffin cells.
The role of protein phosphorylation in catecholamine secretion from bovine adrenomedullary chromaffin cells was studied using different protein kinase inhibitors. Naphthalenesulfonamide derivatives as ML9 and ML7, more specific for the myosin light chain kinase, and the calmodulin antagonist W7 inhibited catecholamine secretion 20 and 40% respectively in digitonin-permeabilized chromaffin cells. ML9 also decreased calcium evoked protein phosphorylation of different proteins including tyrosine hydroxylase in permeabilized cells. These naphthalenesulfonamide derivatives showed also an effect in intact cells, ML9 and W7 produced 50% inhibition in catecholamine secretion and 45Ca2+ uptake, however H8 had no effect. The partial [3H]nitrendipine binding displacement of these drugs to adrenomedullary membranes suggests that these sulfonamide derivatives could interact directly with L-type calcium channels in intact cells. The results obtained in permeabilized cells suggest a possible role of protein phosphorylation in the regulation of catecholamine secretion in chromaffin cells.
Reig
J A
JA
Departamento de Neuroquimica, Facultad de Medicina, Spain.
Viniegra
S
S
Ballesta
J J
JJ
Palmero
M
M
Guitierrez
L M
LM
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002838:Chromaffin System / Q000187:drug effects / Q000378:metabolism*; D004072:Digitonin / Q000494:pharmacology; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides / Q000494:pharmacology*
D001381:Azepines; D002147:Calmodulin; D002395:Catecholamines; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; C056218:ML 9; C017967:W 7; D009219:Myosin-Light-Chain Kinase; D004072:Digitonin; D002118:Calcium