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Cyclic nucleotide-dependent protein kinase and protein kinase C inhibitors H-7 and H-9 fail to inhibit human neutrophil activation

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:6962378
;

The isoquinolinesulfonaminides 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and N-(2-aminoethyl)-5-isoquinolinesulfonamide (H-9) have previously been demonstrated to be potent inhibitors of cyclic nucleotide dependent kinases and protein kinase C while lacking calmodulin antagonist activity. The effects of these compounds on neutrophil functions were examined to determine the role of these kinases in neutrophil activation. At concentrations up to 100 micromolar, H-7 and H-9 compounds failed to inhibit either lysosomal enzyme release or the respiratory burst of neutrophils stimulated with particulate (serum-opsonized zymosan) or soluble (A23187, fMet-Leu-Phe, phorbol myristate acetate) stimuli. In contrast, the calmodulin antagonist N-(6-aminohexyl)-5-chloro-l-naphthalenesulfonamide (W-7) inhibited both the respiratory and secretory responses to the same stimuli. W-5, the nonchlorinated analogue of W-7 which lacks calmodulin antagonist activity, failed to significantly inhibit neutrophil functions. These results suggest that calmodulin-dependent enzymes, rather than cyclic nucleotide-dependent kinases or protein kinase C, may be essential for neutrophil activation.

Research Organization:
Warner-Lambert/Parke-Davis, Ann Arbor, MI
OSTI ID:
6962378
Report Number(s):
CONF-8604222-
Journal Information:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:4; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL FUNCTIONS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
ESTERS
FUNCTIONS
INHIBITION
LEUKOCYTES
MAMMALS
MAN
MATERIALS
NEUTROPHILS
ORGANIC COMPOUNDS
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PRIMATES
TRANSFERASES
VERTEBRATES