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PAF effects on transmembrane signaling pathways in rat kupffer cells

  • PAF and Signal Transduction
  • Published:
Lipids

Abstract

Platelet activating factor (PAF) was found to stimulate the metabolism of inositol phospholipids via deacylation and phospholipase C in Kupffer cells, the resident macrophages in liver. PAF-induced phosphoinositide metabolism occurred in two phases. Within seconds after stimulation, in the absence of extracellular Ca++, platelet activating factor caused the phosphodiester hydrolysis of phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 4-phosphate with the release of inositol 1,4,5-trisphosphate and inositol 1,4-bisphosphate. This was followed by an extracellular Ca++-dependent release of glycerophosphoinositol, inositol monophosphates and inositol bisphosphates. Various Ca++-mobilizing agonists failed to evoke hydrolysis of phosphoinositides. Platelet activating factor also stimulated the synthesis and release of prostaglandins from these cells. Platelet activating factor-stimulated phosphodiester metabolism of phosphoinositides and prostaglandin synthesis was inhibited by treatment with pertussis toxin and cholera toxin. Pertussis toxin also inhibited platelet activating factor-induced glycerophosphoinositol release. Cholera toxin, in contrast, stimulated platelet activating factor-induced glycerophosphoinositol release and prostaglandin synthesis and synergistically stimulated the effect of platelet activating factor on these processes. The results suggest that platelet activating factor-induced metabolism in the Kupffer cells occurs via specific receptors and may be mediated through the activation of different G-proteins.

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Abbreviations

DAG:

diacylglycerol

EGTA:

ethylene glycolbis-(β aminoethyl ether)N,N,N′,N′-tetraacetic acid

GBSS:

Gey's balanced salt solution

GPI:

glycerophosphoinositol

GPIP:

glycerophosphoinositolphosphate

GPIP2 :

glycerophosphoinositolbisphosphate

HPLC:

high performance liquid chromatography

Ins 1-P:

inositol 1-phosphate

Ins 4-P:

inositol 4-phosphate

Ins 1,3-P2 :

inositol 1,3-bisphosphate

Ins 1,4-P2 :

inositol 1,4-bisphosphate

Ins 3,4-P2 :

inositol 3,4-bisphosphate

Ins 1,3,4-P3 :

inositol 1,3,5-trisphosphate

Ins 1,4,5-P3 :

inositol 1,4,5-trisphosphate

Ins 1,3,4,5-P4 :

inositol 1,3,4,5-tetrakisphosphate

PAF:

platelet activating factor (1-O-alkyl-2-acetyl-sn-glycerophosphocholine)

PG:

prostaglandins

PI:

phosphatidylinositol

PIP:

phosphatidylinositol 4-phosphate

PIP2 :

phosphatidylinositol 4,5-bisphosphate

TCA:

trichloroacetic acid

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Authors and Affiliations

  1. Department of Biochemistry, The University of Texas Health Science Center, 7703 Floyd Curl Drive, 78284, San Antonio, TX

    Chandrashekhar R. Gandhi & Merle S. Olson

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  1. Chandrashekhar R. Gandhi
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  2. Merle S. Olson
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Gandhi, C.R., Olson, M.S. PAF effects on transmembrane signaling pathways in rat kupffer cells. Lipids 26, 1038–1043 (1991). https://doi.org/10.1007/BF02536498

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  • DOI: https://doi.org/10.1007/BF02536498

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