Pertussis toxin inhibits chemotactic peptide-stimulated generation of inositol phosphates and lysosomal enzyme secretion in human leukemic (HL-60) cells.
The binding of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine to its cell surface receptor rapidly elicits the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C to form the putative second messengers inositol 1,4,5-trisphosphate and sn-1,2-diacylglycerol. To investigate the possible role of a guanine nucleotide binding protein in transduction of this membrane signal, we examined the effects of pertussis toxin on chemotactic peptide-stimulated inositol phospholipid metabolism in differentiated HL-60 cells labeled with [3H]inositol. Pertussis toxin inhibited the chemotactic tripeptide-stimulated production of inositol mono-, bis-, and trisphosphates and secretion of N-acetyl-beta-D-glucosaminidase in a time- and concentration-dependent manner. Treatment with pertussis toxin did not alter the total incorporation or the distribution of [3H]inositol in inositol phospholipid. Chemotactic peptide receptor number was unchanged, although a slight decrease in binding affinity was observed. These findings suggest a role for a guanine nucleotide binding protein in coupling the chemotactic peptide receptor to phospholipase C.
Brandt
S J
SJ
Dougherty
R W
RW
Lapetina
E G
EG
Niedel
J E
JE
D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001886:Bordetella pertussis; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D007942:Leukemia, Experimental / Q000378:metabolism*; D008247:Lysosomes / Q000201:enzymology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology; D010566:Virulence Factors, Bordetella
D001427:Bacterial Toxins; D010716:Phosphatidylinositols; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D010566:Virulence Factors, Bordetella; D009240:N-Formylmethionine Leucyl-Phenylalanine; D003994:Bucladesine; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D002118:Calcium