Adenosine receptor occupancy suppresses chemoattractant-induced phospholipase D activity by diminishing membrane recruitment of small GTPases.
作者： Nathalie Thibault , Danielle Harbour , Pierre Borgeat , Paul H. Naccache , Sylvain G. Bourgoin
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摘要: Adenosine (Ado) is an important autocrine modulator of neutrophil functions. In this study, we determined the effects endogenous Ado on fMet-Leu-Phe (fMLP)–induced phospholipase D (PLD) activity in neutrophils. The removal extracellular by deaminase (ADA) or blockade its action A2a receptor antagonists 8-(3-chlorostyryl) caffeine (CSC) CGS15943 markedly increased fMLP-induced PLD activation. concentration-dependent stimulatory CSC and were abolished a pretreatment suspensionswith ADA. contrast, selective agonist CGS21680 suppressed Furthermore, inhibition was reversed CGS15943. ADA CGS15943, membrane recruitment cytosolic protein kinase C (PKC), RhoA, ADP-ribosylation factor (ARF) response to fMLP. As shown for activity, effect cofactors translocation cells with Moreover, both PKC, ARF fMLP attenuated antagonized These data demonstrate that released neutrophils milieu inhibits activation blocking association ARF, PKC through occupancy.
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