Potentiation of cytokine induction of group IIA phospholipase A(2) in rat mesangial cells by ATP and adenosine via the A2A adenosine receptor

• Published in: British journal of pharmacology Vol. 132; no. 1; pp. 37 - 46
• Main Authors: Scholz-Pedretti, K, Pfeilschifter, J, Kaszkin, M
• Format: Journal Article
• Language: English
• Published: England 01.01.2001
• Subjects: 5'-Nucleotidase - antagonists & inhibitors; 5'-Nucleotidase - metabolism; Adenosine - metabolism; Adenosine - pharmacology; Adenosine Deaminase - pharmacology; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - metabolism; Adenosine Triphosphate - pharmacology; Animals; Blotting, Northern; Cells, Cultured; Enzyme Induction; Enzyme Inhibitors - pharmacology; Glomerular Mesangium - cytology; Glomerular Mesangium - drug effects; Glomerular Mesangium - metabolism; Group II Phospholipases A2; Interleukin-1 - pharmacology; Phospholipases A - biosynthesis; Purinergic P2 Receptor Antagonists; Rats; Receptor, Adenosine A2A; Receptors, Purinergic P1 - drug effects; RNA, Messenger - biosynthesis; Signal Transduction - drug effects; Suramin - pharmacology; Triazines - pharmacology; Triazoles - pharmacology; Uridine Triphosphate - metabolism; Uridine Triphosphate - pharmacology; Vasodilator Agents - pharmacology
• ISSN: 0007-1188
• DOI: 10.1038/sj.bjp.0703774

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.