Potentiation of cytokine induction of group IIA phospholipase A(2) in rat mesangial cells by ATP and adenosine via the A2A adenosine receptor.
1. In rat mesangial cells extracellular nucleotides were found to increase arachidonic acid release by a cytosolic phospholipase A(2) through the P2Y(2) purinergic receptor. 2. In this study we investigated the effects of ATP and UTP on interleukin-1ss (IL-1ss)-induced mRNA expression and activity of group IIA phospholipase A(2) (sPLA(2)-IIA) in rat mesangial cells. 3. Treatment of cells for 24 h with extracellular ATP potentiated IL-1ss-stimulated sPLA(2)-IIA induction, whereas UTP had no effect. 4. We obtained the following evidence that the P2Y(2) receptor is not involved in the potentiation of sPLA(2)-IIA induction: (i) ATP-gamma-S had no enhancing effect; (ii) suramin, a P(2) receptor antagonist, did not inhibit ATP-mediated potentiation; (iii) inhibition of degradation of extracellular nucleotides by the 5'-ectonucleotidase inhibitor AOPCP did not enhance sPLA(2)-IIA induction and (iv) adenosine deaminase treatment completely abolished the ATP-mediated potentiation of sPLA(2)-IIA induction. 5. In contrast, treatment of mesangial cells with adenosine or the A2A receptor agonist CGS 21680 mimicked the effects of ATP in enhancing IL-1ss-stimulated sPLA(2)-IIA induction, whereas the specific A2A receptor antagonist ZM 241385 completely abolished the potentiating effect of ATP or adenosine. 6. The protein kinase A inhibitor Rp-8-Br-cyclic AMPS dose-dependently inhibited the enhancing effect of ATP or adenosine indicating the participation of an adenosine receptor-mediated cyclic AMP-dependent signalling pathway. 7. These data indicate that ATP mediates proinflammatory long-term effects in rat mesangial cells via its degradation product adenosine through the A2A receptor resulting in potentiation of sPLA(2)-IIA induction.
Scholz-Pedretti
K
K
Pharmazentrum Frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Theodor-Stern-Kai-7, D-60590 Frankfurt am Main, Germany.
Pfeilschifter
J
J
Kaszkin
M
M
D015720:5'-Nucleotidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism / Q000494:pharmacology*; D000243:Adenosine Deaminase / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D054501:Group II Phospholipases A2; D007375:Interleukin-1 / Q000494:pharmacology*; D010741:Phospholipases A / Q000096:biosynthesis*; D058919:Purinergic P2 Receptor Antagonists; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013498:Suramin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D058919:Purinergic P2 Receptor Antagonists; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; D014227:Triazines; D014230:Triazoles; D014665:Vasodilator Agents; C097270:ZM 241385; C022571:adenosine 5'-O-(3-thiotriphosphate); D013498:Suramin; D000255:Adenosine Triphosphate; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D015720:5'-Nucleotidase; D000243:Adenosine Deaminase; D000241:Adenosine; D014544:Uridine Triphosphate