Dissociation of bradykinin-induced prostaglandin formation from phosphatidylinositol turnover in Swiss 3T3 fibroblasts: evidence for G protein regulation of phospholipase A/sub 2/

Journal Article · Tue Sep 01 04:00:00 EDT 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.18.6374· OSTI ID:7253468

Burch, R M; Axelrod, J

In Swiss 3T3 fibroblasts bradykinin stimulated inositol phosphate (InsP) formation and prostaglandin E/sub 2/ (PGE/sub 2/) synthesis. The EC/sub 50/ values for stimulation of PGE/sub 2/ synthesis and InsP formation by bradykinin were similar, 200 pM and 275 pM, respectively. Guanosine-5'-(..gamma..-thio)triphosphate stimulated PGE/sub 2/ synthesis and InsP formation, and guanosine-5'-(..beta..-thio)diphosphate inhibited both PGE/sub 2/ synthesis and InsP formation stimulated by bradykinin. Neither bradykinin-stimulated PGE/sub 2/ synthesis nor InsP formation was sensitive to pertussis toxin. Phorbol ester, dexamethasone, and cycloheximide distinguished between bradykinin-stimulated PGE/sub 2/ synthesis and InsP formation. Phorbol 12-myristate 13-acetate enhanced bradykinin-stimulated PGE/sub 2/ synthesis but inhibited bradykinin-stimulated InsP formation. Pretreatment of cells with dexamethasone for 24 hr inhibited bradykinin-stimulated PGE/sub 2/ synthesis but was without effect on bradykinin-stimulated InsP formation. Cycloheximide inhibited on bradykinin-stimulated InsP formation. When bradykinin was added to cells prelabeled with (/sup 3/H) choline, the phospholipase A/sub 2/ products lysophosphatidylcholine and glycerophosphocholine were generated. The data suggest that bradykinin receptors are coupled by GTP-binding proteins to both phospholipase C and phospholipase A/sub 2/ and that phospholipase A/sub 2/ is the enzyme that catalyzes release of arachidonate for prostaglandin synthesis.

• Research Organization: National Institute of Mental Health, Bethesda, MD (USA)
• OSTI ID: 7253468
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:18; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ALCOHOLS
AMINES
AMMONIUM COMPOUNDS
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOCHEMISTRY
BIOLOGICAL EFFECTS
BIOSYNTHESIS
BRADYKININ
CARBOHYDRATES
CARBOXYLESTERASES
CARCINOGENS
CHEMISTRY
CHOLINE
CONNECTIVE TISSUE CELLS
CORTICOSTEROIDS
CYCLOHEXIMIDE
DEXAMETHASONE
DRUGS
ENZYMES
ESTERASES
ESTERS
FIBROBLASTS
FUNGICIDES
GLUCOCORTICOIDS
HYDROLASES
HYDROXY COMPOUNDS
INOSITOLS
KETONES
KININS
LABELLED COMPOUNDS
LIPASE
LIPOTROPIC FACTORS
MONOSACCHARIDES
ORGANIC COMPOUNDS
PEPTIDES
PESTICIDES
PHORBOL ESTERS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHOTRANSFERASES
POLYPEPTIDES
PREGNANES
PROSTAGLANDINS
PROTEINS
QUATERNARY COMPOUNDS
SACCHARIDES
SOMATIC CELLS
STEROIDS
SYNTHESIS
TRANSFERASES
TRITIUM COMPOUNDS