Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

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-
Conference Information:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:4
Country of Publication:
United States
Language:
English

Similar Records

Role of protein kinase C (PKC) and calmodulin in histamine release (HR) from human basophils induced by anti-IGE, tri-peptide, A23187 and PMA
Conference · Fri Feb 28 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) · OSTI ID:5382471
Activation and regulation of arachidonic acid release in rabbit peritoneal neutrophils
Thesis/Dissertation · Thu Dec 31 23:00:00 EST 1987 · OSTI ID:7189609
Inhibition of protein kinase C induces differentiation in Neuro-2a cells
Journal Article · Fri Jun 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States) · OSTI ID:5322544

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