Guanine Nucleotide-Dependent Release of Arachidonic Acid in Permeabilized Inflammatory Cells
Phosphoinositide metabolism has been known to play a crucial role in signal transduction systems of various cells, producing two second messengers (Nishizuka 1984; Berridge and Irvine, 1984). One is 1,2-diacylglycerol (1,2-DG), which directly activates protein kinase C., and the other is inositol-l,4,5-trisphosphate, which releases Ca2+ from internal storage sites. Recently, several lines of evidence have been revealing the involvement of guanine nucleotide-binding regulatory protein (G protein) in agonist-induced activation of phospholipase C., analogous to the adenylate cyclase system (Cockcroft, 1987; Haslam and Davidson, 1984; Cockcroft and Gomperts, 1985; Bradford and Rubin, 1986; Brasset al., 1986; Kikuchiet al., 1986; Lapetina, 1986). Upon stimulation of various types of inflammatory cells, arachidonic acid is released and converted to physiologically active substances, prostaglandins and leukotrienes. Although the coupling of phospholipase C with G protein has been inten sively studied, only limited information is available regarding the involvement of G protein in phospholipase A2activation (Burchet al., 1986; Jelsema, 1987; Benjaminet al., 1987; Nakashimaet al., 1987). Possible involvement of G protein in phospholipase A2activation was investigated by examining the effects of guanine nucleotides (GTP or its nonhydrolyzable analog, GTPγS) on generation of free arachidonic acid in permeabilized inflammatory cells, including saponin-permeabilized human platelets and ATP-permeabilized rat peritoneal mast cells.
KeywordsArachidonic Acid Human Platelet Guanine Nucleotide Pertussis Toxin Arachidonic Acid Release
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