Document Detail


Cell-specific differential modulation of human trabecular meshwork cells by selective adenosine receptor agonists.
MedLine Citation:
PMID:  17070802     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Activation of A1 and A2A subtype adenosine receptors (AR) likely exert opposing effects on outflow of aqueous humor, and thereby, on intraocular pressure. Selective agonists of adenosine receptor (AR) subtypes have previously been applied to trabecular meshwork (TM) and Schlemm's canal (SC) cells to identify the site(s) of differential purinergic modulation. However, the apparent changes in volume monitored by previously measuring projected cell area might have partially reflected cell contraction and relaxation. In addition, whole-cell current responses of the TM cells previously described were highly variable following application of selective A1, A2A and A3 agonists. The complexity of the electrophysiologic responses may have reflected cell heterogeneity of the populations harvested from collagenase digestion of TM explants. We now report measurements of TM-cell volume using calcein fluorescence quenching, an approach independent of contractile state. Furthermore, we have applied selective AR agonists to a uniform population of human TM cells, the hTM5 cell line. A1, but not A2A or A3, AR agonists triggered TM-cell shrinkage. Both A1 and A2A AR agonists produced reproducible increases in TM-cell whole-cell currents of similar magnitude. The results suggest that previous measurements of explant-derived TM cells may have reflected a range of responses from phenotypically different cell populations, and that the opposing effects of A1 and A2A agonists on outflow resistance are not likely to be mediated by actions on a single population of TM cells. These opposing effects might reflect AR responses by two or more subpopulations of TM cells, by TM and SC cells or by inner-wall SC cells, alone.
Authors:
Mike O Karl; Kim Peterson-Yantorno; Mortimer M Civan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-10-30
Journal Detail:
Title:  Experimental eye research     Volume:  84     ISSN:  0014-4835     ISO Abbreviation:  Exp. Eye Res.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-11-28     Completed Date:  2007-02-26     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  0370707     Medline TA:  Exp Eye Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  126-34     Citation Subset:  IM    
Affiliation:
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine A1 Receptor Agonists
Adenosine A2 Receptor Agonists
Adenosine A3 Receptor Agonists
Aqueous Humor / physiology
Calcium / metabolism
Cell Size / drug effects
Dose-Response Relationship, Drug
Humans
Ion Transport / physiology
Patch-Clamp Techniques
Potassium / metabolism
Purinergic P1 Receptor Agonists*
Receptor, Adenosine A1 / metabolism
Receptor, Adenosine A2A / metabolism
Receptor, Adenosine A3 / metabolism
Receptors, Purinergic P1 / metabolism,  physiology
Trabecular Meshwork / cytology*,  drug effects,  metabolism
Grant Support
ID/Acronym/Agency:
EY013624/EY/NEI NIH HHS; EY01583/EY/NEI NIH HHS; R01 EY013624/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Adenosine A1 Receptor Agonists; 0/Adenosine A2 Receptor Agonists; 0/Adenosine A3 Receptor Agonists; 0/Purinergic P1 Receptor Agonists; 0/Receptor, Adenosine A1; 0/Receptor, Adenosine A2A; 0/Receptor, Adenosine A3; 0/Receptors, Purinergic P1; 7440-09-7/Potassium; 7440-70-2/Calcium
Comments/Corrections

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