Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.59 (MIP)
 4,906 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extracellular nucleotides are primary signals for tissue injury, acting together with various chemical mediators such as prostanoids at the inflammatory site. We investigated whether prostaglandin E2 (PGE2) affects purinergic signaling in murine J774 macrophages. J774 cells expressed four different purinoceptor mRNAs: the ionotropic P2X4 and P2X7 receptors and G-protein-coupled P2Y2 and P2Y6 receptors. Functional responses mediated by these purinoceptor subtypes were confirmed by measurement of intracellular Ca2+ concentration ([Ca2+]i) in fura-2-loaded cells. Thus, low concentrations (10 microM) of ATP (P2Y2 agonist) and UDP (P2Y6 agonist) evoked Ca2+ transient in a phospholipase C (PLC)-dependent manner, whereas the P2X7 agonist benzoylbenzoyl-ATP (BzATP, 500 microM) caused a sustained rise in [Ca2+]i. Furthermore, ivermectin, an activator of the P2X4-receptor channel, enhanced the ATP-induced [Ca2+]i elevation. PGE2 inhibited ATP- and UDP-induced [Ca2+]i elevation, without affecting the BzATP-induced sustained [Ca2+]i elevation. Stimulation of J774 cells by UDP or BzATP increased the production of macrophage inflammatory peptide-alpha (MIP-alpha). PGE2 abolished the UDP-induced MIP-alpha production, but not the BzATP-induced one. These results demonstrate that purinergic signalings in macrophages were regulated by PGE2 in a subtype-specific manner. The different inhibitory effects on distinct purinoceptor functions may be related to the anti-inflammatory property of PGE2.
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PMID:Regulation of purinergic signaling by prostaglandin E2 in murine macrophages. 1867 87

In this study, we investigated the role of extracellular nucleotides in chemokine (KC, MIP-2, MCP-1, and CXCL10) expression and secretion by murine primary intestinal epithelial cells (IECs) with a focus on P2Y6 receptors. qRT-PCR experiments showed that P2Y6 was the dominant nucleotide receptor expressed in mouse IEC. In addition, the P2Y6 ligand UDP induced expression and secretion of CXCL10. For the other studies, we took advantage of mice deficient in P2Y6 (P2ry6-/-). Similar expression levels of P2Y1, P2Y2, P2X2, P2X4, and A2A were detected in P2ry6-/- and WT IEC. Agonists of TLR3 (poly(I:C)), TLR4 (LPS), P2Y1, and P2Y2 increased the expression and secretion of CXCL10 more prominently in P2ry6-/- IEC than in WT IEC. CXCL10 expression and secretion induced by poly(I:C) in both P2ry6-/- and WT IEC were inhibited by general P2 antagonists (suramin and Reactive-Blue-2), by apyrase, and by specific antagonists of P2Y1, P2Y2, P2Y6 (only in WT), and P2X4. Neither adenosine nor an A2A antagonist had an effect on CXCL10 expression and secretion. Macrophage chemotaxis was induced by the supernatant of poly(I:C)-treated IEC which was consistent with the level of CXCL10 secreted. Finally, the non-nucleotide agonist FGF2 induced MMP9 mRNA expression also at a higher level in P2ry6-/- IEC than in WT IEC. In conclusion, extracellular nucleotides regulate CXCL10 expression and secretion by IEC. In the absence of P2Y6, these effects are modulated by other P2 receptors also present on IEC. These data suggest that the presence of P2Y6 regulates chemokine secretion and may also regulate IEC homeostasis.
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PMID:P2Y6 Receptors Regulate CXCL10 Expression and Secretion in Mouse Intestinal Epithelial Cells. 2954 Oct 27