Adenosine stimulates Cl- channels of nonpigmented ciliary epithelial cells.
Ciliary epithelial cells possess multiple purinergic receptors, and occupancy of A1 and A2 adenosine receptors is associated with opposing effects on intraocular pressure. Aqueous adenosine produced increases in short-circuit current across rabbit ciliary epithelium, blocked by removing Cl- and enhanced by aqueous Ba2+. Adenosine's actions were further studied with nonpigmented ciliary epithelial (NPE) cells from continuous human HCE and ODM lines and freshly dissected bovine cells. With gramicidin present, adenosine (> or = 3 microM) triggered isosmotic shrinkage of the human NPE cells, which was inhibited by the Cl- channel blockers 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) and niflumic acid. At 10 microM, the nonmetabolizable analog 2-chloroadenosine and AMP also produced shrinkage, but not inosine, UTP, or ATP. 2-Chloroadenosine (> or = 1 microM) triggered increases of whole cell currents in HCE cells, which were partially reversible, Cl- dependent, and reversibly inhibited by NPPB. Adenosine (> or = 10 microM) also stimulated whole cell currents in bovine NPE cells. We conclude that occupancy of adenosine receptors stimulates Cl- secretion in mammalian NPE cells.
Carré
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DA
Department of Physiology, The University of Pennsylvania, Philadelphia 19104-6085, USA.
Mitchell
C H
CH
Peterson-Yantorno
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K
Coca-Prados
M
M
Civan
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MM
D015762:2-Chloroadenosine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology*; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D002924:Ciliary Body / Q000502:physiology*; D006096:Gramicidin / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009544:Niflumic Acid / Q000494:pharmacology; D009579:Nitrobenzoates / Q000494:pharmacology; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000502:physiology*; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D018118:Chloride Channels; D009579:Nitrobenzoates; D018047:Receptors, Purinergic P1; D006096:Gramicidin; D015762:2-Chloroadenosine; D001464:Barium; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D000249:Adenosine Monophosphate; D009544:Niflumic Acid; D000241:Adenosine