Functional PAF receptors in glia cells: binding parameters and regulation of expression.
Platelet activating factor is a unique phosphoglycerine which possesses a variety of biological functions exerting its biological effects via specific surface receptors. In the central nervous system, platelet activating factor has been suggested to play a role during injury especially in conditions of ischemia and trauma-induced neuronal damage. The specific cell populations expressing platelet activating factor receptor, however, have not been identified. In this study, the binding properties of platelet activating factor receptors in C6 glioma cells and primary cultures of astrocytes and oligodendrocytes were characterized by using the ligand [3H]WEB 2086. Early-passage glial cells which exhibit oligodendrocytic phenotype, expressed lower levels of [3H]WEB 2086 binding than either late-passage cells which exhibit astrocytic phenotypes or primary astroglia cells. No specific binding was observed in primary cultures of oligodendrocytes. The Bmax (136 +/- 15.3 fmol/mg protein) and Kd (29 +/- 3.2 nM) levels obtained for primary astroglia cells were similar to those described for other cell types. The expression of platelet activating factor receptor in early-passage glia cells was up-regulated by treatment with insulin which induces astrocytic differentiation. In contrast, db-cyclic AMP exerted an inhibitory effect on the level of platelet activating factor receptor in both early- and late-passage cells. The level of functional platelet activating factor receptor in C6 cells as measured by the ability of platelet activating factor to induce 45Ca2+ influx was increased in cells expressing astrocytic phenotypes and was decreased in db-cyclic AMP-treated cells. In accordance with lack of specific [3H]WEB 2086 binding, platelet activating factor did not induce a detectable response of Ca2+ influx in cultures of oligodendrocytes. This report provides the first direct demonstration of selective expression of functional platelet activating factor receptors and their properties in astroglia cells. The findings support the suggestion that platelet activating factor may play an important role as a mediator of injury and immune responses in the nervous system.
Brodie
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Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001381:Azepines / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles / Q000378:metabolism
D001381:Azepines; D002132:Calcium Radioisotopes; D007328:Insulin; D009419:Nerve Tissue Proteins; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D003994:Bucladesine; D002118:Calcium