ATP reduces macromolecule permeability of endothelial monolayers despite increasing [ Ca

نویسندگان

  • T. NOLL
  • H. HÖLSCHERMANN
  • K. KOPREK
  • D. GÜNDÜZ
  • W. HABERBOSCH
  • H. TILLMANNS
  • H. M. PIPER
چکیده

Noll, T., H. Hölschermann, K. Koprek, D. Gündüz, W. Haberbosch, H. Tillmanns, and H. M. Piper. ATP reduces macromolecule permeability of endothelial monolayers despite increasing [Ca]i. Am. J. Physiol. 276 (Heart Circ. Physiol. 45): H1892–H1901, 1999.—We investigated the relationship between theATP-evoked rise of cytosolic Ca21 concentration ([Ca]i) and barrier function in porcine aortic endothelial monolayers. ATP (0.01–100 μM) induced a transient rise of [Ca]i and reduced permeability in a concentrationdependent manner. In contrast, the Ca21 ionophore ionomycin (1 μM) elicited a rise in [Ca]i comparable to that induced by ATP (10 μM), but it increased permeability. For the reduction of permeability, nucleotides were found to be in the following order of potency: ATP 5 ATPgS . ADP 5 UTP. Blockade of adenosine receptors by 8-phenyltheophylline (10 μM) did not affect ATP (10 μM)-induced reduction of permeability. ATP reduced permeability even in endothelial monolayers that had been loaded with the Ca21 chelator BAPTA to prevent the rise in [Ca]i. U-73122 (1 μM), an inhibitor of phospholipase C (PLC), completely abolished the effect of ATP (10 μM) on permeability. It also abolished the translocation of protein kinase C (PKC) in response to ATP, which could also be achieved by the PKC inhibitors Gö-6976 (100 nM) or bisindolylmaleimide I (1 μM). In the presence of PKC inhibitors, however, the permeability effect of ATP was not affected. The presence of inhibitors of adenylate or guanylate cyclase (50 μM SQ-22536 or 20 μM ODQ) prevented changes in cyclic nucleotides but did not affect the permeability effects of ATP. The study shows that ATP reduces macromolecule permeability via a PLC-mediated mechanism that is independent of the concomitant effects of ATP on cytosolic Ca21, cyclic nucleotides, or PKC.

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تاریخ انتشار 1999