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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 · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5382471
; ;

The transmission of messages from plasma membrane receptors into intracellular biochemical events occurs thru the generation and modulation of various second messengers. In the basophil, multiple stimuli induce Hr and the release of other mediators. Various biochemical events, including protein kinase C activation, have been proposed as essential. The authors studied the effects of PKC inhibitors H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) and H-9 (N-(2-aminoethyl)-5-isoquinolinesulfonamide) and calmodulin inhibitors W-7 and perphenazine on HR induced by anti-IgE, fmlp, A23187 and phorbol myristate acetate (PMA - a direct activator of PKC). At concentrations up to 100 mcM, H-7 and H-9 were completely without effect on anti-IgE, fmlp and A23187 induced HR. PMA induced release was completely inhibited by H-7 (IC/sub 50/ = 40 mcM) and H-9 (IC/sub 50/ = 21 mcM). In contrast, all four stimuli were inhibited by W-7 (all with IC/sub 50/s < 50 mcM) and perphenazine (all with IC/sub 50/s < 33 mcM). These results suggest that calmodulin dependent reactions are common and critical to the activation-secretion coupling of basophils while PKC activation is essential only for the PMA-induced secretory response.

Research Organization:
Warner-Lambert/Parke-Davis Pharmaceutical Research, Ann Arbor, MI
OSTI ID:
5382471
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. 45:3; ISSN FEPRA
Country of Publication:
United States
Language:
English

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Related Subjects

550200 -- Biochemistry
560301* -- Chemicals Metabolism &amp; Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
AZOLES
BASOPHILS
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARCINOGENS
CELL CONSTITUENTS
CELL MEMBRANES
ENZYME INHIBITORS
ENZYMES
ESTERS
HETEROCYCLIC COMPOUNDS
HISTAMINE
IMIDAZOLES
LEUKOCYTES
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PEPTIDES
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
PROTEINS
RECEPTORS
SECRETION
TRANSFERASES