Document Detail


Common actions of adenosine receptor agonists in modulating human trabecular meshwork cell transport.
MedLine Citation:
PMID:  12879160     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A(1) adenosine receptors (ARs) reduce, and A(2)ARs increase intraocular pressure, partly by differentially altering resistance to aqueous humor outflow. It is unknown whether the opposing effects of A(1)AR and A(2)AR agonists are mediated at different outflow-pathway cell targets or by opposing actions on a single cell target. We tested whether a major outflow-pathway cell, the trabecular meshwork (TM) cell might constitute the primary AR-agonist target and respond differentially to A(1), A(2A) and A(3)AR agonists. Receptor activation in human TM cells was identified by applying subtype-selective AR agonists: CPA and ADAC for A(1)ARs, CGS 21680 and DPMA for A(2A)ARs, and Cl-IB-MECA and IB-MECA for A(3)ARs. Stimulation of A(1), A(2A) and A(3)ARs elevated Ca(2+), measured with fura-2. Whole-cell patch clamping indicated that AR agonists activated ion channels non-uniformly, possibly reflecting variability in magnitude of agonist-triggered second-messenger responses. A(1), A(2A) and A(3)AR agonists all reduced volume, determined by calcein cell imaging. The endogenous source of adenosine delivery to the outflow pathway could be the TM cells since these cells were stimulated to release ATP by hypotonic perfusion. We conclude that: (1) TM cells express functional A(1), A(2A) and A(3)ARs; and (2) the reported differential effects of AR agonists on aqueous humor outflow are not mediated by differential actions on TM-cell Ca(2+) and volume, but likely by actions on separate cell targets.
Authors:
J C Fleischhauer; C H Mitchell; W D Stamer; M O Karl; K Peterson-Yantorno; M M Civan
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of membrane biology     Volume:  193     ISSN:  0022-2631     ISO Abbreviation:  J. Membr. Biol.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-07-24     Completed Date:  2004-01-26     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0211301     Medline TA:  J Membr Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  121-36     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 / metabolism
Adenosine Triphosphate / metabolism
Aqueous Humor / drug effects*,  physiology*
Calcium / metabolism
Calcium Signaling / drug effects
Cell Line
Cell Size / drug effects
Humans
Intracellular Fluid / metabolism
Ion Channels / drug effects
Receptor, Adenosine A1 / agonists
Receptor, Adenosine A3 / agonists
Receptors, Adenosine A2 / agonists
Receptors, Purinergic P1 / agonists*
Trabecular Meshwork / cytology,  drug effects*,  physiology*
Grant Support
ID/Acronym/Agency:
EY013624/EY/NEI NIH HHS; EY01583/EY/NEI NIH HHS; EY12797/EY/NEI NIH HHS; EY13434/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Ion Channels; 0/Receptor, Adenosine A1; 0/Receptor, Adenosine A3; 0/Receptors, Adenosine A2; 0/Receptors, Purinergic P1; 56-65-5/Adenosine Triphosphate; 58-61-7/Adenosine; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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