Potential role for a guanine nucleotide regulatory protein in chemoattractant receptor mediated polyphosphoinositide metabolism, Ca++ mobilization and cellular responses by leukocytes

Margrith W. Verghese, Charles D. Smith, Ralph Snyderman

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

Islet activating protein from Bordetella pertussis toxin which ribosylates certain guanine nucleotide regulatory proteins causes a marked reduction of chemoattractant-elicited responses such as chemotaxis, 02 production and cAMP elevations in human polymorphonuclear leukocytes. The toxin appears to exert its effects by preventing the rapid breakdown of phosphatidylinositol 4,5-bisphosphate induced by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine, thereby inhibiting the increase in intracellular [Ca++] which normally follows chemoattractant stimulation. Responses of leukocytes exposed to Concanavalin A, the Ca++ ionophore A23187, or phorbol myristate acetate were not affected by the toxin. Thus the chemoattractant receptor appears to be coupled to a phosphoinositide specific phospholipase C through a guanine nucleotide regulatory protein. We propose that this complex of receptor-guanine nucleotide regulatory protein-phospholipase C may be applicable to the class of receptors which mobilize intracellular Ca++ by stimulating polyphosphoinositide breakdown.

Original languageEnglish (US)
Pages (from-to)450-457
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume127
Issue number2
DOIs
StatePublished - Mar 15 1985

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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