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Receptor-recognized alpha 2-macroglobulin-methylamine elevates intracellular calcium, inositol phosphates and cyclic AMP in murine peritoneal macrophages.

Publication ,  Journal Article
Misra, UK; Chu, CT; Rubenstein, DS; Gawdi, G; Pizzo, SV
Published in: Biochem J
March 15, 1993

Human plasma alpha 2-macroglobulin (alpha 2M) is a tetrameric proteinase inhibitor, which undergoes a conformational change upon reaction with either a proteinase or methylamine. As a result, a receptor recognition site is exposed on each subunit of the molecule enabling it to bind to its receptors on macrophages. We have used Fura-2-loaded murine peritoneal macrophages and digital video fluorescence microscopy to examine the effects of receptor binding on second messenger levels. alpha 2M-methylamine caused a rapid 2-4-fold increase in intracellular Ca2+ concentration ([Ca2+]i) within 5 s of binding to receptors. The agonists induced a focal increase in [Ca2+]i that spread out to other areas of the cell. The increase in [Ca2+]i was dependent on the alpha 2M-methylamine concentration and on the extracellular [Ca2+]. Both sinusoidal and transitory oscillations were observed, which varied from cell to cell. Neither alpha 2M nor boiled alpha 2M-methylamine, forms that are not recognized by the receptor, affected [Ca2+]i in peritoneal macrophages under identical conditions of incubation. The alpha 2M-methylamine-induced rise in [Ca2+]i was accompanied by a rapid and transient increase in macrophage inositol phosphates, including inositol tris- and tetrakis-phosphates. Native alpha 2M did not stimulate a rise in inositol phosphates. Finally, binding of alpha 2M-methylamine to macrophages increased cyclic AMP transiently. Thus receptor-recognized alpha-macroglobulins behave as agonists whose receptor binding causes stimulation of signal transduction pathways.

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Published In

Biochem J

DOI

ISSN

0264-6021

Publication Date

March 15, 1993

Volume

290 ( Pt 3)

Issue

Pt 3

Start / End Page

885 / 891

Location

England

Related Subject Headings

  • alpha-Macroglobulins
  • Peritoneal Cavity
  • Microscopy, Fluorescence
  • Mice, Inbred C57BL
  • Mice
  • Methylamines
  • Macrophages
  • Inositol Phosphates
  • Humans
  • Fura-2
 

Citation

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Misra, U. K., Chu, C. T., Rubenstein, D. S., Gawdi, G., & Pizzo, S. V. (1993). Receptor-recognized alpha 2-macroglobulin-methylamine elevates intracellular calcium, inositol phosphates and cyclic AMP in murine peritoneal macrophages. Biochem J, 290 ( Pt 3)(Pt 3), 885–891. https://doi.org/10.1042/bj2900885
Misra, U. K., C. T. Chu, D. S. Rubenstein, G. Gawdi, and S. V. Pizzo. “Receptor-recognized alpha 2-macroglobulin-methylamine elevates intracellular calcium, inositol phosphates and cyclic AMP in murine peritoneal macrophages.Biochem J 290 ( Pt 3), no. Pt 3 (March 15, 1993): 885–91. https://doi.org/10.1042/bj2900885.
Misra UK, Chu CT, Rubenstein DS, Gawdi G, Pizzo SV. Receptor-recognized alpha 2-macroglobulin-methylamine elevates intracellular calcium, inositol phosphates and cyclic AMP in murine peritoneal macrophages. Biochem J. 1993 Mar 15;290 ( Pt 3)(Pt 3):885–91.
Misra, U. K., et al. “Receptor-recognized alpha 2-macroglobulin-methylamine elevates intracellular calcium, inositol phosphates and cyclic AMP in murine peritoneal macrophages.Biochem J, vol. 290 ( Pt 3), no. Pt 3, Mar. 1993, pp. 885–91. Pubmed, doi:10.1042/bj2900885.
Misra UK, Chu CT, Rubenstein DS, Gawdi G, Pizzo SV. Receptor-recognized alpha 2-macroglobulin-methylamine elevates intracellular calcium, inositol phosphates and cyclic AMP in murine peritoneal macrophages. Biochem J. 1993 Mar 15;290 ( Pt 3)(Pt 3):885–891.
Journal cover image

Published In

Biochem J

DOI

ISSN

0264-6021

Publication Date

March 15, 1993

Volume

290 ( Pt 3)

Issue

Pt 3

Start / End Page

885 / 891

Location

England

Related Subject Headings

  • alpha-Macroglobulins
  • Peritoneal Cavity
  • Microscopy, Fluorescence
  • Mice, Inbred C57BL
  • Mice
  • Methylamines
  • Macrophages
  • Inositol Phosphates
  • Humans
  • Fura-2