Nerve growth factor-stimulated calcium uptake into PC12 cells: uniqueness of the channel and evidence for phosphorylation.
Nerve growth factor stimulates the uptake of radioactive calcium into PC12 cells. This stimulation is inhibited by low concentrations of dideoxyforskolin or staurosporine, and by high concentrations of nifedipine or cadmium. On the other hand, neither dideoxyforskolin nor staurosporine inhibited the stimulation of calcium uptake caused by BK-8644 or adenosine triphosphate (ATP). Nickel inhibited only the effect of ATP on calcium uptake, and actually stimulated the effects of either BK-8644 or nerve growth factor. Down-regulation of L-calcium channels by BK-8644 blocked the subsequent stimulation of calcium uptake by this agent, but not the stimulation by nerve growth factor. Conversely, pre-treatment of the cells with nerve growth factor inhibited the subsequent stimulation of calcium uptake by nerve growth factor, but not the stimulation by BK-8644. The effects of BK-8644 and nerve growth factor on calcium uptake were additive, as were the effects of nerve growth factor and ATP. Phosphatase 2A inhibited the effect of nerve growth factor on calcium uptake, but did not influence the action of BK-8644. On the other hand, calcineurin inhibited the effect of BK-8644 on calcium uptake, but potentiated the action of nerve growth factor. Calmidazolium or fluphenazine also inhibited the effect of nerve growth factor on calcium uptake, but okadaic acid stimulated it. A comparison of the effects of these inhibitors on the actions of various calcium channel agonists shows that the channels on which the action of nerve growth factor is exerted are different than either the L-type calcium channels or the ATP-activated calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Nikodijevic
B
B
Section on Growth Factors, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Guroff
G
G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000085:Acetates; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology; D019703:Calcineurin; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002148:Calmodulin-Binding Proteins / Q000494:pharmacology; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D010749:Phosphoprotein Phosphatases / Q000494:pharmacology; D010766:Phosphorylation; D054648:Protein Phosphatase 2
D000085:Acetates; D015220:Calcium Channels; D002132:Calcium Radioisotopes; D002148:Calmodulin-Binding Proteins; D009414:Nerve Growth Factors; D002104:Cadmium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; C028031:cadmium acetate; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D009543:Nifedipine; D002118:Calcium