Nerve Growth Factor Amplifies Cyclic AMP Production in the HT4 Neuronal Cell Line

Kelly A. Berg, Saul Maayani, Ronald McKay, William P. Clarke

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Abstract: There has been considerable interest and controversy in the relationship between nerve growth factor (NGF) and the cyclic AMP (cAMP) second messenger system. We have used a novel, neuronal cell line (HT4) to investigate the effect of NGF on the adenylyl cyclase signaling system. Treatment of cells with NGF (100 ng/ml 15 min) amplified cAMP accumulation (≈75%) in response to activation of adenosine A2 receptors (5 min) with 5′‐N‐ethylcarboxamidoadenosine or activation of adenylyl cyclase directly with forskolin. Basal cAMP accumulation was not altered by NGF. This amplification appears to be mediated by activation of protein kinase C (PKC) because (1) it was mimicked by activators (phorbol esters and a diacylglycerol analogue) of PKC, (2) the effects of NGF and phorbol ester on cAMP accumulation were not additive, (3) NGF amplification of cAMP accumulation was abolished by down‐regulation of PKC, (4) NGF increased cytosolic PKC activity, and (5) inhibitors of PKC blocked the NGF‐induced amplification of cAMP accumulation. Although NGF‐induced amplification of cAMP accumulation was dependent upon PKC, mechanisms other than the classic activation pathway (i.e., hydrolysis of inositol phospholipids or the production of diacylglycerol) appeared to mediate PKC activation by NGF. The tyrosine kinase inhibitor, lavendustin A, blocked NGF‐mediated amplification of cAMP accumulation, suggesting a novel interaction between a tyrosine kinase and protein kinase C.

Original languageEnglish (US)
Pages (from-to)220-228
Number of pages9
JournalJournal of Neurochemistry
Volume64
Issue number1
DOIs
StatePublished - Jan 1995

Keywords

  • Cross talk
  • Cyclic AMP
  • Nerve growth factor
  • Protein kinase C
  • Tyrosine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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