Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2011;28(6):1135-44.
doi: 10.1159/000335865. Epub 2011 Dec 16.

Mechanisms of ATP release, the enabling step in purinergic dynamics

Ang Li  1 , Juni Banerjee, Chi Ting Leung, Kim Peterson-Yantorno, W Daniel Stamer, Mortimer M Civan
Affiliations
Review

Mechanisms of ATP release, the enabling step in purinergic dynamics

Ang Li et al. Cell Physiol Biochem. 2011.

Abstract

The only effective intervention to slow onset and progression of glaucomatous blindness is to lower intraocular pressure (IOP). Among other modulators, adenosine receptors (ARs) exert complex regulation of IOP. Agonists of A(3)ARs in the ciliary epithelium activate Cl(-) channels, favoring increased formation of aqueous humor and elevated IOP. In contrast, stimulating A(1)ARs in the trabecular outflow pathway enhances release of matrix metalloproteinases (MMPs) from trabecular meshwork (TM) cells, reducing resistance to outflow of aqueous humor to lower IOP. These opposing actions are thought to be initiated by cellular release of ATP and its ectoenzymatic conversion to adenosine. This view is now supported by our identification of six ectoATPases in trabecular meshwork (TM) cells and by our observation that external ATP enhances TM-cell secretion of MMPs through ectoenzymatic formation of adenosine. ATP release is enhanced by cell swelling and stretch. Also, enhanced ATP release and downstream MMP secretion is one mediator of the action of actin depolymerization to reduce outflow resistance. Inflow and outflow cells share pannexin-1 and connexin hemichannel pathways for ATP release. However, vesicular release and P2X(7) release pathways were functionally limited to inflow and outflow cells, respectively, suggesting that blocking exocytosis might selectively inhibit inflow, lowering IOP.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Purinergic regulation of aqueous humor dynamics. Swelling or stretching of cells releases ATP, which can then be converted by ectoATPases to adenosine. Activation of A3 adenosine receptors of NPE cells of the ciliary epithelium will activate Cl− channels, favoring enhanced inflow and elevating IOP. In contrast, adenosine delivered to the trabecular meshwork cells of the outflow pathway activates A1 adenosine receptors, stimulating secretion of matrix metalloproteinases−2 and −9, lowering outflow resistance and IOP.
Fig. 2
Fig. 2
Comparison of swelling-activated pathways for ATP release in outflow and inflow cells. The inhibitors and, in parentheses, the release-pathway targets are presented along the abscissa. The numbers of wells studied are indicated for both outflow and inflow cells. P2X7 receptors mediated ATP release only in TM cells, whereas vesicular ATP release was displayed only by ciliary epithelial (CE) cells.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Quigley HA. Number of people with glaucoma worldwide. Br J Ophthalmol. 1996;80:389–393. - PMC - PubMed
    1. Collaborative Normal-Tension Glaucoma Study Group The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1998;126:498–505. - PubMed
    1. Collaborative Normal-Tension Glaucoma Study Group Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol. 1998;126:487–497. - PubMed
    1. The AGIS investigators: The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130:429–440. - PubMed
    1. Kass MA, Heuer DK, Higginbotham EJ, Johnson CA, Keltner JL, Miller JP, Parrish RK, 2nd, Wilson MR, Gordon M. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120:701–713. discussion 829-730. - PubMed

Publication types

MeSH terms

Substances