Common actions of adenosine receptor agonists in modulating human trabecular meshwork cell transport.
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.
Fleischhauer
J C
JC
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104-6085, USA.
Mitchell
C H
CH
Stamer
W D
WD
Karl
M O
MO
Peterson-Yantorno
K
K
Civan
M M
MM
D000241:Adenosine / Q000378:metabolism; D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D058909:Adenosine A3 Receptor Agonists; D000255:Adenosine Triphosphate / Q000378:metabolism; D001082:Aqueous Humor / Q000187:drug effects* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D048429:Cell Size / Q000187:drug effects; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D058906:Purinergic P1 Receptor Agonists; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*
D058907:Adenosine A1 Receptor Agonists; D058908:Adenosine A2 Receptor Agonists; D058909:Adenosine A3 Receptor Agonists; D007473:Ion Channels; D058906:Purinergic P1 Receptor Agonists; D000255:Adenosine Triphosphate; D000241:Adenosine; D002118:Calcium