title: Effect of cAMP on short-circuit current in isolated human ciliary body.
abstract: BACKGROUND
  Cyclic adenosine monophosphate (cAMP) could activate chloride channels in bovine ciliary body and trigger an increase in the ionic current (short-circuit current, Isc) across the ciliary processes in pigs. The purpose of this study was to investigate how cAMP modulates Isc in isolated human ciliary processes and the possible involvement of chloride transport across the tissue in cAMP-induced Isc change.
  
  
  METHODS
  In an Ussing-type chamber system, the Isc changes induced by the cAMP analogue 8-bromo-cAMP and an adenylyl cyclase activator forskolin in isolated human ciliary processes were assessed. The involvement of Cl(-) component in the bath solution was investigated. The effect of Cl(-) channel (10 µmol/L niflumic acid and 1 mmol/L 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)), K(+) channel (10 mmol/L tetraethylammonium chloride (TEA)), or Na(+) channel blockers (1 mmol/L amiloride) on 8-bromo-cAMP-induced Isc change was also studied.
  
  
  RESULTS
  Dose-dependently, 8-bromo-cAMP (10 nmol/L-30 µmol/L) or forskolin (10 nmol/L-3 µmol/L) increased Isc across the ciliary processes with an increase in negative potential difference on the non-pigmented epithelium (NPE) side of the tissue. Isc increase induced by 8-bromo-cAMP was more pronounced when the drug was applied on the NPE side than on the pigmented epithelium side. When the tissue was bathed in low Cl(-) solutions, the Isc increase was significantly inhibited. Finally, niflumic acid and DIDS, but not TEA or amiloride, significantly prevented the Isc increase induced by 8-bromo-cAMP.
  
  
  CONCLUSIONS
  cAMP stimulates stroma-to-aqueous anionic transport in isolated human ciliary processes. Chloride is likely to be among the ions, the transportation of which across the tissue is triggered by cAMP, suggesting the potential role of cAMP in the process of aqueous humor formation in human eyes.
authors.affiliation: Chinese University of Hong Kong, Shantou, Guangdong, China. wubasel@hotmail.com
authors.forename: Ren-yi
authors.initials: RY
authors.lastname: Wu
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Qian-qian
authors.initials: QQ
authors.lastname: Hu
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors; D002924:Ciliary Body / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology
chemical_list: D018118:Chloride Channels; D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP