Mechanisms of ATP release, the enabling step in purinergic dynamics

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

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1135-1144
Number of pages10
JournalCellular Physiology and Biochemistry
Volume28
Issue number6
DOIs
StatePublished - 2011
Externally publishedYes

Keywords

  • Actin cytoskeleton
  • Ciliary epithelium
  • Connexin hemichannels
  • Intraocular pressure
  • Pannexin-1 hemichannels
  • Trabecular meshwork
  • Vesicular release

ASJC Scopus subject areas

  • Physiology

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