Nerve growth factor-induced differentiation of PC12 cells is accompanied by elevated adenylyl cyclase activity.
Rat pheochromocytoma (PC12) cells characteristically undergo differentiation when cultured with nerve growth factor (NGF). Here we show that NGF dramatically increased the adenylyl cyclase-activating property of forskolin in PC12 cells. This effect of NGF was well maintained even when NGF was removed after 4 days, even though the morphological features of neuronal differentiation were rapidly lost on removal of NGF. The enhanced cAMP production in response to forskolin could be due to a synergistic interaction between forskolin and endogenously released agonists acting on G(s)-coupled receptors. However, responses to forskolin were not attenuated by antagonists of adenosine A2 receptors or pituitary adenylate cyclase-activating polypeptide (PACAP) receptors, suggesting that adenosine and PACAP were not involved. Adenylyl cyclases 3, 6 and 9 were the predominant isoforms expressed in PC12 cells, but we found no evidence for NGF-induced changes in expression levels of any of the 9 adenylyl cyclase isoforms, nor in the expression of Gα(s). These findings highlight that NGF has a subtle influence on adenylyl cyclase activity in PC12 cells which may influence more than the neurite extension process classically associated with neuronal differentiation.
Yung
H S
HS
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, SAR, China.
Lai
K H
KH
Chow
K B S
KB
Ip
N Y
NY
Tsim
K W K
KW
Wong
Y H
YH
Wu
Z
Z
Wise
H
H
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects / Q000502:physiology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014316:Tritium / Q000378:metabolism
D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D020033:Protein Isoforms; D014316:Tritium; D005576:Colforsin; D020932:Nerve Growth Factor; D000242:Cyclic AMP; D000262:Adenylyl Cyclases