Cyclic AMP regulation of arachidonic acid (AA) release and phospholipid metabolism in human monocytes: modulation by intracellular calcium

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5272559

Hoffstein, S T; Manzi, R M; Godfrey, R W

Stimulation of inflammatory cells by specific ligands results in activation of phospholipase(s) and production of oxygenation products of AA. The authors have employed (/sup 3/H)AA labeled monocytes to examine the involvement of cAMP in regulating phospholipase activity as measured by percent of incorporated (/sup 3/H)AA released and TLC analysis of (/sup 3/H)AA cellular lipids. Maximum release of radiolabel (31 +/- 5%) occurred upon challenge with the calcium ionophore A23187/sup -/ (10..mu..M), while FMLP (1..mu..M) yielded 15 +/- 1% and untreated cells 8 +/- 1%. Pretreatment of monocytes with isobutyl methyl xanthine/sup -/(IBMX) or dibutyrl cyclic AMP (d-cAMP) inhibited FMLP stimulated release with IC/sub 50/'s of 2.5 x 10/sup -5/M and 8 x 10/sup -5/M respectively. Exposure of monocytes to maximal levels of IBMX (5 x 10/sup -4/M) or d-cAMP (10/sup -3/M) also reduced release from controls by 40%, while A23187 induced release was uneffected by either. Examination of (/sup 3/H) AA labeled phospholipids showed that phosphatidylcholine (PC) and phosphatidylinositol were the major pools labeled and that stimulation by FMLP or A23187 appeared to deplete the PC pool exclusively. Prior exposure to IBMX or d-cAMP inhibited the loss from the PC pool only in untreated or FMLP stimulated cells. The data suggests that a phospholipase A/sub 2/ activity, directly primarily towards PC, is regulated by cAMP possibly by inhibiting receptor mediated increases in intracellular calcium levels.

• Research Organization: Smith Kline and French Labs., Philadelphia, PA
• OSTI ID: 5272559
• Report Number(s): CONF-8606151-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH METALS
AMP
ARACHIDONIC ACID
AROMATICS
AZAARENES
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CALCIUM
CARBOXYLESTERASES
CARBOXYLIC ACIDS
ELEMENTS
ENZYME ACTIVITY
ENZYMES
ESTERASES
ESTERS
HETEROCYCLIC COMPOUNDS
HYDROLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LEUKOCYTES
LIGANDS
LIPASE
LIPIDS
MATERIALS
METABOLISM
METALS
MONOCARBOXYLIC ACIDS
MONOCYTES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHOSPHOLIPIDS
PURINES
SECRETION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
XANTHINES