Activation of cyclic nucleotide formation in murine neuroblastoma N1E-115 cells by modified human thrombins

R. M. Snider, M. McKinney, J. W. Fenton, E. Richelson

Research output: Contribution to journalArticle

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Abstract

The activity of α-thrombin and chemically modified derivatives of this enzyme in stimulating cGMP formation in murine neuroblastoma clone N1E-115 cells is reported. The rank order potency of the compounds falls into three classes: 1) α-thrombin is the most potent and effective; 2) the catalytically active enzymes γ-thrombin, trypsin, and nitro-α-thrombin are approximately 50-fold less potent than α-thrombin; and 3) active site blocked derivatives of α-thrombin are 100 to 1000-fold less potent than α-thrombin. Native α-thrombin consistently produces the most effective response, usually 1.5 to 3-fold greater than any of the other compounds tested. Preincubation of cells with quinacrine, an inhibitor of phospholipase ∅ 2, or with the lipoxygenase inhibitors 5,8,11,14-eicosatetraynoic acid or nordihydroguaiaretic acid prior to thrombin challenge resulted in a concentration-dependent attenuation of the response. Indomethacin was without effect in modifying the response. These results suggest that thrombin stimulation of neuroblastoma cells involves the release of arachidonic acid and its metabolism by lipoxygenase. These results clearly demonstrate the activity of α-thrombin in stimulating a receptor-mediated response in cultured nerve cells. The results are discussed in relation to the interaction of endogenous α-thrombin with nerve cells following invasive trauma and to the possible presence of endogenous proteinases with a neurotransmitter-like function.

Original languageEnglish (US)
Pages (from-to)9078-9081
Number of pages4
JournalJournal of Biological Chemistry
Volume259
Issue number14
StatePublished - 1984

Fingerprint

Cyclic Nucleotides
Neuroblastoma
Thrombin
Chemical activation
Neurons
5,8,11,14-Eicosatetraynoic Acid
Masoprocol
Derivatives
Quinacrine
Lipoxygenase Inhibitors
Lipoxygenase
Phospholipases
Enzymes
Arachidonic Acid
Metabolism
Indomethacin
Trypsin
Neurotransmitter Agents
Cultured Cells
Catalytic Domain

ASJC Scopus subject areas

  • Biochemistry

Cite this

Snider, R. M., McKinney, M., Fenton, J. W., & Richelson, E. (1984). Activation of cyclic nucleotide formation in murine neuroblastoma N1E-115 cells by modified human thrombins. Journal of Biological Chemistry, 259(14), 9078-9081.

Activation of cyclic nucleotide formation in murine neuroblastoma N1E-115 cells by modified human thrombins. / Snider, R. M.; McKinney, M.; Fenton, J. W.; Richelson, E.

In: Journal of Biological Chemistry, Vol. 259, No. 14, 1984, p. 9078-9081.

Research output: Contribution to journalArticle

Snider, RM, McKinney, M, Fenton, JW & Richelson, E 1984, 'Activation of cyclic nucleotide formation in murine neuroblastoma N1E-115 cells by modified human thrombins', Journal of Biological Chemistry, vol. 259, no. 14, pp. 9078-9081.
Snider, R. M. ; McKinney, M. ; Fenton, J. W. ; Richelson, E. / Activation of cyclic nucleotide formation in murine neuroblastoma N1E-115 cells by modified human thrombins. In: Journal of Biological Chemistry. 1984 ; Vol. 259, No. 14. pp. 9078-9081.
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