Potentiation of cytokine induction of group IIA phospholipase A2 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-1 beta (IL-1 beta)-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-1 beta -stimulated sPLA(2)-IIA induction, whereas UTP had no effect. 4 We obtained the following evidence that the P2Y2 receptor is not involved in the potentiation of sPLA2-IIA induction: (i) ATP-gamma -S had no enhancing effect; (ii) suramin, a P2 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 sPLA2-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-1 beta -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.