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Title: Activation and regulation of arachidonic acid release in rabbit peritoneal neutrophils

Arachidonic acid release in rabbit neutrophils can be enhanced by the addition of chemotactic fMet-Leu-Phe, platelet-activating factor, PAF, or the calcium ionophore A23187. Over 80% of the release ({sup 3}H)arachidonic acid comes from phosphatidylcholine and phosphatidylinositol. The release is dose-dependent and increases with increasing concentration of the stimulus. The A23187-induced release increases with increasing time of the stimulation. ({sup 3}H)arachidonic acid release, but not the rise in the concentration of intracellular calcium, is inhibited in pertussis toxin-treated neutrophils stimulated with PAF. The ({sup 3}H)arachidonic acid released by A23187 is potentiated while that release by fMET-Leu-Phe or PAF is inhibited in phorbol 12-myristate 13-acetate, PMA, treated rabbit neutrophils. The protein kinase C inhibitor 1-(5-isoquinoline sulfonyl)-2-methylpiperazine, H-7, has no effect on the potentiation by PMA of the A23187-induced release, it prevents the inhibition by PMA of the release produced by PAF or fMet-Leu-Phe. In addition, PMA increases arachidonic acid release in H-7-treated cells stimulated with fMet-Leu-Phe. The diacylglycerol kinase inhibitor R59022 increases the level of diacylglycerol in neutrophils stimulated with fMet-Leu-Phe. Furthermore, R59022 potentiates ({sup 3}H) arachidonic acid release produced by fMet-Leu-Phe. This potentiation is not inhibited by H-7, in fact, it is increased in H-7-treated neutrophils.
Authors:
Publication Date:
OSTI Identifier:
7189609
Resource Type:
Miscellaneous
Resource Relation:
Other Information: Thesis (Ph. D.)
Publisher:
Storrs, CT (US); Univ. of Connecticut
Research Org:
Connecticut Univ., Storrs, CT (USA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; ARACHIDONIC ACID; SECRETION; BLOOD COAGULATION FACTORS; BIOLOGICAL FUNCTIONS; PHORBOL ESTERS; BIOLOGICAL EFFECTS; DOSE-RESPONSE RELATIONSHIPS; ENZYME INHIBITORS; NEUTROPHILS; PHOSPHOLIPIDS; RABBITS; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMALS; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CARBOXYLIC ACIDS; CARCINOGENS; COAGULANTS; DRUGS; ESTERS; FUNCTIONS; HEMATOLOGIC AGENTS; HYDROGEN COMPOUNDS; ISOTOPE APPLICATIONS; LEUKOCYTES; LIPIDS; MAMMALS; MATERIALS; MONOCARBOXYLIC ACIDS; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC PHOSPHORUS COMPOUNDS; PROTEINS; VERTEBRATES 560300* -- Chemicals Metabolism & Toxicology; 550501 -- Metabolism-- Tracer Techniques