title: Nerve growth factor-induced differentiation of PC12 cells is accompanied by elevated adenylyl cyclase activity.
abstract: 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.
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, SAR, China.
authors.forename: H S
authors.initials: HS
authors.lastname: Yung
authors.forename: K H
authors.initials: KH
authors.lastname: Lai
authors.forename: K B S
authors.initials: KB
authors.lastname: Chow
authors.forename: N Y
authors.initials: NY
authors.lastname: Ip
authors.forename: K W K
authors.initials: KW
authors.lastname: Tsim
authors.forename: Y H
authors.initials: YH
authors.lastname: Wong
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Wise
mesh_terms: 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
chemical_list: D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D020033:Protein Isoforms; D014316:Tritium; D005576:Colforsin; D020932:Nerve Growth Factor; D000242:Cyclic AMP; D000262:Adenylyl Cyclases