Characteristics of the K-252a-induced increase in calcium uptake in PC12 cells.
K-252a treatment produced a 30-50% increase in the uptake of radioactive calcium by PC12 cells within 3-4 minutes. The increase in uptake was partially blocked by inhibitors of voltage-operated calcium channels, such as nifedipine, but not by inhibitors of receptor-operated calcium channels, such as nickel or suramin. Introduction of phosphatase 2A into the cells completely blocked the effect of K-252a. Long-term treatment of the cells with either K-252a or with nerve growth factor blocked the subsequent actions of either K-252a or nerve growth factor on calcium uptake, but neither altered the subsequent action of the L-channel agonist Bay K 8644 on calcium uptake. Calcium uptake was not stimulated by K-252a in PC12nnr, cells that have little or no high-affinity nerve growth factor receptors; cells expressing increased levels of high-affinity nerve growth factor receptors showed a response to K-252a comparable to that seen in parent PC12. The data suggest that the increased uptake of radioactive calcium produced by K-252a is mediated by a mechanism very similar to that serving the increased calcium uptake produced by nerve growth factor.
Nikodijevic
B
B
Section on Growth Factors, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Aschkenasy
M
M
Dickens
G
G
Lachance
C
C
Guroff
G
G
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002227:Carbazoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D026121:Indole Alkaloids; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats
D002227:Carbazoles; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D002104:Cadmium; C049985:staurosporine aglycone; D011493:Protein Kinase C; D009543:Nifedipine; D002118:Calcium