TY - JOUR
T1 - Potential role for a guanine nucleotide regulatory protein in chemoattractant receptor mediated polyphosphoinositide metabolism, Ca++ mobilization and cellular responses by leukocytes
AU - Verghese, Margrith W.
AU - Smith, Charles D.
AU - Snyderman, Ralph
PY - 1985/3/15
Y1 - 1985/3/15
N2 - 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.
AB - 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.
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U2 - 10.1016/S0006-291X(85)80181-9
DO - 10.1016/S0006-291X(85)80181-9
M3 - Article
C2 - 2983721
AN - SCOPUS:0022386314
SN - 0006-291X
VL - 127
SP - 450
EP - 457
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -