Platelet‐activating factor increases inositol phosphate production and cytosolic free Ca2+ concentrations in cultured rat Kupffer cells

FEBS Letters

Bhalla, Ramesh C.¹  Sharma, Ram V.¹  Fisher, Rory A.² 

[1] Department of Pharmacology, The University of Iowa, College of Medicine, Iowa City, IA 52242, USA;Department of Anatomy, The University of Iowa, College of Medicine, Iowa City, IA 52242, USA

关键词: Platelet-activating factor;    Phospholipase C;    Inositol phosphate;    Ca2+;    (Liver;    Kupffer cell);    PAF;    platelet-activating factor;    [Ca2+]i;    free cytosolic Ca2+ concentration;    PMA;    4β-phorbol 12β-myristate 13α-acetate;    M199;    medium 199;    BSS;    Earl's balanced salt solution;   

DOI  :  10.1016/0014-5793(89)81421-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Platelet-activating factor (PAF) stimulates glycogenolysis in perfused livers but not in isolated hepatocytes [(1984) J. Biol. Chem. 259, 8685–8688]. PAF-induced glycogenolysis in liver is associated closely with a pronounced constriction of the hepatic vasculature [(1986) J. Biol. Chem. 261, 644–649]. These and other observations suggest that PAF stimulates glycogenolysis in liver indirectly by interactions with cells other than hepatocytes. We have evaluated effects of PAF on hepatic Kupffer cells, which regulate flow through the hepatic sinusoids. Application of PAF to [³H]inositol-labeled Kupffer cells produced dose-dependent increases in [³H]inositol phosphates with an EC₅₀ value of 4 × 10⁻¹⁰ M. Increasesin inositol phosphate production in response to PAF were inhibited by a specific PAF receptor antagonist, SRI 63-675 (2 × 10⁻⁷ M), and stimulus of protein kinase C, phorbol 12-myristate 13-acetate (1 × 10⁻⁷ M). Measurements of cytosolic free Ca²⁺ concentrations ([Ca²⁺]_i) in single Kupffer cells loaded with Fura-2 demonstrated that application of PAF (2 × 10⁻⁹ M) resulted in significant increases in [Ca²⁺]_i. These observations lead us to propose that interactions of PAF with Kupffer cells may result in the hemodynamic and metabolic responses to PAF in liver.

【 授权许可】

Unknown