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Regulation of Leukocyte Responses to Chemoattractants: Role of Receptors, Guanine Nucleotide Regulatory (N) Proteins and Phospholipase C

  • Conference paper
Molecular Mechanisms of Desensitization to Signal Molecules

Part of the book series: NATO ASI Series ((ASIH,volume 6))

Abstract

Guanine nucleotides regulate the the affinity of formylpeptide chemoattractant receptors on leukocytes suggesting that these receptors might be coupled to an N protein. Chemoattractant receptors, however do not regulate the activity of adenylate cyclase. Since Ca2+ mobilization is vital for polymorphonuclear leukocyte (PMN) activation, the possibility that chemoattractant receptors might utilize an N protein to activate the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP­2), thereby releasing the Ca2+ mobilizer, inositol 1,4,5-trisphosphate (IP3), and the protein kinase C activator 1,2-diacylglycerol was explored. Bordetella pertussis toxin (PT), an agent which specifically ADP-ribosylates and inhibits the activity of certain N proteins, ribosylates a 40 kDA protein in human PMNs and monocytes. PT blocks the ability of chemoattractants to induce Chemotaxis, O2 - production and lysosomal enzyme secretion. PT, moreover, prevents chemoattractants from mobilizing intracellular Ca2+ and hydrolyzing PIP2.

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Author information

Authors and Affiliations

  1. Howard Hughes Medical Institute, and Department of Medicine, Duke University Medical Center, Durham, North Carolina, 27710, USA

    Charles D. Smith, Margarith W. Verghese & Ralph Snyderman

Authors
  1. Charles D. Smith
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  2. Margarith W. Verghese
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  3. Ralph Snyderman
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Editor information

Editors and Affiliations

  1. Zoölogisch Laboratorium, Kaiserstraat 63, Postbus 9516, 2300 RA, Leiden, The Netherlands

    T. M. Konijn  & P. J. M. Van Haastert  & 

  2. Van Beethovenlaan 5, 3161 RV, Rhoon, The Netherlands

    H. Van der Wel

  3. Molecular Pharmacology Group, Department of Biochemistry, University of Glasgow, G12 8QQ, Glasgow, Scotland

    M. D. Houslay

  4. Kennistransfer, University of Leiden, Stationsweg 46, Postbus 9500, 2300 RA, Leiden, The Netherlands

    H. Van der Starre

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© 1987 Springer-Verlag Berlin Heidelberg

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Smith, C.D., Verghese, M.W., Snyderman, R. (1987). Regulation of Leukocyte Responses to Chemoattractants: Role of Receptors, Guanine Nucleotide Regulatory (N) Proteins and Phospholipase C. In: Konijn, T.M., Van der Wel, H., Van Haastert, P.J.M., Houslay, M.D., Van der Starre, H. (eds) Molecular Mechanisms of Desensitization to Signal Molecules. NATO ASI Series, vol 6. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-71782-6_18

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  • DOI: https://doi.org/10.1007/978-3-642-71782-6_18

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-71784-0

  • Online ISBN: 978-3-642-71782-6

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