May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Effects of dinucleotides polyphosphates in trabecular meshwork cells and outflow facility
Author Affiliations & Notes
  • X. Gasull
    Lab. Neurofisiologia, Facultat de Medicina–IDIBAPS, University of Barcelona, Barcelona, Spain
  • D. Soto
    Lab. Neurofisiologia, Facultat de Medicina–IDIBAPS, University of Barcelona, Barcelona, Spain
  • A. Peral
    Dept. Óptica,
    E.U. Óptica, Universidad Complutense de Madrid, Madrid, Spain
  • A. Gual
    Lab. Neurofisiologia, Facultat de Medicina–IDIBAPS, University of Barcelona, Barcelona, Spain
  • J. Pintor
    Dept. Bioquímica,
    E.U. Óptica, Universidad Complutense de Madrid, Madrid, Spain
  • Footnotes
    Commercial Relationships  X. Gasull, None; D. Soto, None; A. Peral, None; A. Gual, None; J. Pintor, None.
  • Footnotes
    Support  PM99–0169, BFI2003–01190, UCMA–E017, SSAF2003–00338
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 5028. doi:
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      X. Gasull, D. Soto, A. Peral, A. Gual, J. Pintor; Effects of dinucleotides polyphosphates in trabecular meshwork cells and outflow facility . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5028.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Nucleotides and dinucleotides are natural compounds present in the aqueous humor. Previous studies (J Pharmacol Exp Therap 304; 342–8. 2003) have shown the presence of diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) in aqueous humor. When applied topically, Ap4A decreased IOP while Ap5A increased it. Since dinucleotides polyphosphate stimulate P2Y purinergic receptors we studied their presence in trabecular meshwork (TM) cells and the effect of diadenosine polyphosphates (ApnAs, n=3–5) and Up4U in outflow facility (C). Methods: Cellular studies were performed in bovine TM cells from primary cultures. Western blotting and immunocytochemistry techniques were used to detect the presence of P2Y receptors. Intracellular calcium concentration ([Ca2+]i) was measured in TM cells loaded with Fura–2. Outflow facility studies were performed in bovine anterior segments perfused at constant pressure. Results: Western blot and immunocytochemistry revealed the expression of P2Y1, P2Y2 and P2Y4 receptors in TM cells. [Ca2+]i increments were seen when stimulating TM cells with Ap3A, Ap4A, Ap5A and Up4U. Nevertheless, the percentage and the pattern of response were different for each of them. % of response EC50 values were 11, 61, 39 and 0.68 µM, respectively. Regarding the [Ca2+]i increments, Up4U produced the most important [Ca2+]i mobilization. Calcium peaks ranged between 203 and 667 nM. Perfusion with 1 µM Ap3A or Ap4A increased C whereas perfusion with 1 µM Up4U or Ap5A did not change it significantly. Conclusions: These results demonstrate the presence of P2Y1, P2Y2 and P2Y4 purinergic receptors in TM cells. Intracellular calcium experiments demonstrate that the P2Y2 agonist Up4U was the most potent agonist to increase [Ca2+]i being the effects of Ap3A, Ap4A and Ap5A smaller. Our results show that the reducing effect of Ap4A on IOP may be mediated by an increase in C. The effects of Ap4A (P2Y1, P2Y2 and P2Y4 agonist) and Up4A (P2Y2 and P2Y4 agonist) suggest that the C increase could be mediated by P2Y1 activation.

Keywords: outflow: trabecular meshwork • trabecular meshwork • receptors: pharmacology/physiology 
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