Calmodulin- and protein phosphorylation-independent release of catecholamines from PC-12 cells.
Catecholamine secretion from PC-12 cells can be triggered by agents that increase intracellular Ca2+ and is enhanced by phorbol esters and agents that elevate intracellular cAMP concentrations. In mutant PC-12 cells lacking cAMP-dependent protein kinase (PK-A) in which protein kinase C (PK-C) was down-regulated, Ca2+-dependent secretion occurred normally but was no longer enhanced by cAMP or phorbol esters. In digitonin-permeabilized PC-12 cells that lacked PK-C and PK-A, a range of calmodulin (CaM) inhibitors failed to block Ca2+-triggered catecholamine release. Moreover, Mn2+, a CaM activator, failed to trigger catecholamine release whereas Ba2+, which does not activate CaM, supported secretion. These results indicate that the basic mechanism of stimulus/secretion coupling in PC-12 cells does not absolutely require a regulated protein phosphorylation- or calmodulin-dependent step.
Matthies
H J
HJ
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Palfrey
H C
HC
Miller
R J
RJ
D000310:Adrenal Gland Neoplasms; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002413:Cations, Divalent; D002460:Cell Line; D002463:Cell Membrane Permeability; D004072:Digitonin / Q000494:pharmacology; D007700:Kinetics; D009154:Mutation; D010673:Pheochromocytoma; D011494:Protein Kinases / Q000378:metabolism*
D002121:Calcium Channel Blockers; D002147:Calmodulin; D002395:Catecholamines; D002413:Cations, Divalent; D011494:Protein Kinases; D004072:Digitonin; D002118:Calcium