Lipoxin A sub 4 antagonizes cellular and in vivo actions of leukotriene D sub 4 in rat glomerular mesangial cells: Evidence for competition at a common receptor

Journal Article · Mon May 01 00:00:00 EDT 1989 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.86.9.3438· OSTI ID:5353072

Badr, K F; DeBoer, D K; Schwartzberg, M; Serhan, C N ^[1]

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1. Vanderbilt Univ. School of Medicine, Nashville, TN (USA)

Lipoxin A{sub 4} (LXA{sub 4}) was competitive with ({sup 3}H)leukotriene D{sub 4} (LTD{sub 4}) for specific binding to cultured rat glomerular mesangial cells. Half-maximal inhibition was obtained with 100 nM LXA{sub 4}, compared with 10 nM for unlabeled LTD{sub 4}. At 10 and 50 nM LXA{sub 4} induced low, but significant, increases in mesangial-cell inositol trisphosphate generation: 48% and 44% increases as compared to vehicle controls, respectively (compared with 146% and 106% increments obtained for equimolar LTD{sub 4}), which were abolished in the presence of 100-fold concentrations of the LTD{sub 4} receptor antagonist, SKF 104353. To test the in vivo relevance of these results, the authors established a dose-response curve for the reducing effects of intrarenal arterial LTD{sub 4} on glomerular filtration rate and renal plasma flow in anesthetized rats without or with LXA{sub 4}. Mean percent decreases in glomerular filtration rate/renal plasma flow during LTD{sub 4} administration were measured. The results show LXA{sub 4} competes for ({sup 3}H)LTD{sub 4} binding to mesangial cells, its presence prevents LTD{sub 4}-induced inositol trisphosphate generation, and its own stimulation of mesangial-cell inositol trisphosphate is blocked by an LTD{sub 4} receptor antagonist. These results suggest that LTD{sub 4} and LXA{sub 4} interact at a common site on rat mesangial cells at which LXA{sub 4} provokes partial agonist responses and competitively antagonizes both the cellular and physiological actions of LTD{sub 4}. Moreover, these results provide evidence for a potential counterregulatory interaction between leukotrienes and lipoxins that may be relevant during glomerular inflammation.

• OSTI ID: 5353072
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 86:9; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ARACHIDONIC ACID
BIOCHEMICAL REACTION KINETICS
BIOCHEMISTRY
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARBOHYDRATES
CARBOXYLIC ACIDS
CHEMISTRY
DOSE-RESPONSE RELATIONSHIPS
ENZYMES
GLOMERULI
HYDROGEN COMPOUNDS
INHIBITION
INOSITOL
INOSITOLS
ISOTOPE APPLICATIONS
KIDNEYS
KINETICS
LEUKOCYTES
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MONOCARBOXYLIC ACIDS
MONOSACCHARIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDOREDUCTASES
OXYGENASES
PROTEINS
RADIORECEPTOR ASSAY
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SACCHARIDES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES