A3 adenosine receptors regulate Cl- channels of nonpigmented ciliary epithelial cells

Am J Physiol. 1999 Mar;276(3):C659-66. doi: 10.1152/ajpcell.1999.276.3.C659.


Adenosine stimulates Cl- channels of the nonpigmented (NPE) cells of the ciliary epithelium. We sought to identify the specific adenosine receptors mediating this action. Cl- channel activity in immortalized human (HCE) NPE cells was determined by monitoring cell volume in isotonic suspensions with the cationic ionophore gramicidin present. The A3-selective agonist N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) triggered shrinkage (apparent Kd = 55 +/- 10 nM). A3-selective antagonists blocked IB-MECA-triggered shrinkage, and A3-antagonists (MRS-1097, MRS-1191, and MRS-1523) also abolished shrinkage produced by 10 microM adenosine when all four known receptor subtypes are occupied. The A1-selective agonist N6-cyclopentyladenosine exerted a small effect at 100 nM but not at higher or lower concentrations. The A2A agonist CGS-21680 triggered shrinkage only at high concentration (3 microM), an effect blocked by MRS-1191. IB-MECA increased intracellular Ca2+ in HCE cells and also stimulated short-circuit current across rabbit ciliary epithelium. A3 message was detected in both HCE cells and rabbit ciliary processes using RT-PCR. We conclude that human HCE cells and rabbit ciliary processes possess A3 receptors and that adenosine can activate Cl- channels in NPE cells by stimulating these A3 receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Adult
  • Animals
  • Chloride Channels / metabolism*
  • Ciliary Body / cytology
  • Ciliary Body / drug effects
  • Ciliary Body / metabolism*
  • Ciliary Body / physiology
  • Electric Conductivity
  • Epithelial Cells / metabolism*
  • Humans
  • Iris / drug effects
  • Iris / physiology
  • Male
  • Purinergic P1 Receptor Agonists
  • RNA, Messenger / metabolism
  • Rabbits
  • Receptors, Purinergic P1 / metabolism
  • Receptors, Purinergic P1 / physiology*


  • Chloride Channels
  • Purinergic P1 Receptor Agonists
  • RNA, Messenger
  • Receptors, Purinergic P1
  • N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine
  • Adenosine