Similarity of A(3)-adenosine and swelling-activated Cl(-) channels in nonpigmented ciliary epithelial cells.
Chloride release from nonpigmented ciliary epithelial (NPE) cells is a final step in forming aqueous humor, and adenosine stimulates Cl(-) transport by these cells. Whole cell patch clamping of cultured human NPE cells indicated that the A(3)-selective agonist 1-deoxy-1-(6-[([3-iodophenyl]methyl)amino]-9H-purin-9-yl)-N-methyl-be ta-D-ribofuranuronamide (IB-MECA) stimulated currents (I(IB-MECA)) by approximately 90% at +80 mV. Partial replacement of external Cl(-) with aspartate reduced outward currents and shifted the reversal potential (V(rev)) from -23 +/- 2 mV to -0.0 +/- 0.7 mV. Nitrate substitution had little effect. Perfusion with the Cl(-) channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and niflumic acid inhibited the currents. Partial Cl(-) replacement with aspartate and NO(3)(-), and perfusion with NPPB, had similar effects on the swelling-activated whole cell currents (I(Swell)). Partial cyclamate substitution for external Cl(-) inhibited inward and outward currents of both I(IB-MECA) and I(Swell). Both sets of currents also showed outward rectification and inactivation at large depolarizing potentials. The results are consistent with the concept that A(3)-subtype adenosine agonists and swelling activate a common population of Cl(-) channels.
Carré
D A
DA
Department of Physiology, School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Mitchell
C H
CH
Peterson-Yantorno
K
K
Coca-Prados
M
M
Civan
M M
MM
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D018118:Chloride Channels; D058906:Purinergic P1 Receptor Agonists; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D000241:Adenosine