![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
|
|
|
|
|
||
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication February 22, 2005.
Revised June 7, 2005.
Accepted for publication June 7, 2005.
The most important risk factor for the development of glaucoma is elevated intraocular pressure (IOP). Hypotensive drugs decrease IOP preventing optic nerve damage and further vision loss. The balance between aqueous humor (AH) production and drainage determines IOP, and problems in AH outflow pathways are associated with open-angle glaucoma development. Previous studies have shown the presence of diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) in the AH. Topic application of Ap4A to the cornea decreased IOP while Ap5A increased it. Since dinucleoside polyphosphates stimulate P2Y purinergic receptors, we studied their presence in trabecular meshwork (TM) cells. Additionally, the effects of diadenosine polyphosphates (ApnAs, n=3-5) and Up4U (INS365) in outflow facility were tested. P2Y1, P2Y2 and P2Y4 receptors were detected in TM cells by western blot and immunocytochemistry. In TM cells, Ap3A, Ap4A and Ap5A induced discrete [Ca2+]i mobilizations compared with higher and more sustained [Ca2+]i mobilizations after Up4U application. In bovine ocular anterior segments perfused at constant pressure, 1µM Ap3A or Ap4A increased outflow facility, whereas Up4U or Ap5A did not modify it. 2-MeSADP, a selective P2Y1 agonist, induced outflow facility increases similar to those obtained after Ap3A and Ap4A, and these were prevented by addition of the selective P2Y1 receptor antagonist MRS2179. Our results demonstrate that the hypotensive effect of Ap4A and other dinucleotides is mediated, at least in part, by increasing trabecular outflow facility through activation of P2Y1 receptors. The latter would appear to be an interesting target in the development of antiglaucomatous drugs to selectively increase AH outflow.
Key words:
aqueous humor, calcium, dinucleotides, glaucoma, purinergic P2Y receptors, trabecular meshwork
This article has been cited by other articles:
|
|
 |
|
  C. Mayo, R. Ren, C. Rich, M. A. Stepp, and V. Trinkaus-Randall Regulation by P2X7: Epithelial Migration and Stromal Organization in the Cornea Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4384 - 4391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Abad, G. Lorente, N. Gavara, M. Morales, A. Gual, and X. Gasull Activation of Store-Operated Ca2+ Channels in Trabecular Meshwork Cells Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 677 - 686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. E. Tovell and J. Sanderson Distinct P2Y Receptor Subtypes Regulate Calcium Signaling in Human Retinal Pigment Epithelial Cells Invest. Ophthalmol. Vis. Sci., January 1, 2008; 49(1): 350 - 357. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Mediero, A. Peral, and J. Pintor Dual roles of diadenosine polyphosphates in corneal epithelial cell migration. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4500 - 4506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Burnstock Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol. Rev., March 1, 2006; 58(1): 58 - 86. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
