Nerve growth factor amplifies cyclic AMP production in the HT4 neuronal cell line

Kelly A Berg, S. Maayani, R. McKay, William P Clarke

Research output: Contribution to journalArticle

11 Citations (Scopus)

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
StatePublished - 1995

Fingerprint

Nerve Growth Factor
Cyclic AMP
Protein Kinase C
Cells
Cell Line
Amplification
Chemical activation
Diglycerides
Phorbol Esters
Adenylyl Cyclases
Protein-Tyrosine Kinases
Adenosine A2 Receptors
Adenosine-5'-(N-ethylcarboxamide)
Neurotrophin 3
Second Messenger Systems
Colforsin
Phosphatidylinositols
Hydrolysis
Down-Regulation

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Nerve growth factor amplifies cyclic AMP production in the HT4 neuronal cell line. / Berg, Kelly A; Maayani, S.; McKay, R.; Clarke, William P.

In: Journal of Neurochemistry, Vol. 64, No. 1, 1995, p. 220-228.

Research output: Contribution to journalArticle

Berg, Kelly A ; Maayani, S. ; McKay, R. ; Clarke, William P. / Nerve growth factor amplifies cyclic AMP production in the HT4 neuronal cell line. In: Journal of Neurochemistry. 1995 ; Vol. 64, No. 1. pp. 220-228.
@article{e31a02f14dc849fea9f202c569e61ff1,
title = "Nerve growth factor amplifies cyclic AMP production in the HT4 neuronal cell line",
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.",
keywords = "Cross talk, Cyclic AMP, Nerve growth factor, Protein kinase C, Tyrosine kinase",
author = "Berg, {Kelly A} and S. Maayani and R. McKay and Clarke, {William P}",
year = "1995",
language = "English (US)",
volume = "64",
pages = "220--228",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Nerve growth factor amplifies cyclic AMP production in the HT4 neuronal cell line

AU - Berg, Kelly A

AU - Maayani, S.

AU - McKay, R.

AU - Clarke, William P

PY - 1995

Y1 - 1995

N2 - 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.

AB - 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.

KW - Cross talk

KW - Cyclic AMP

KW - Nerve growth factor

KW - Protein kinase C

KW - Tyrosine kinase

UR - http://www.scopus.com/inward/record.url?scp=0028830731&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028830731&partnerID=8YFLogxK

M3 - Article

VL - 64

SP - 220

EP - 228

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 1

ER -