cGMP modulates transport across the ciliary epithelium

cGMP reduced the short-circuit current (I _SC) when applied to the aqueous surface of isolated rabbit and cat ciliary epithelia. cGMP either stimulated (in the rabbit) or had no effect (in the cat) on I _SC when applied to the stromal surface. Addition of the cGMP-mediated hormone atrial natriuretic peptide (ANP) to the stromal (but not the aqueous) surface, or the nitrovasodilator sodium nitroprusside to the stromal surface, inhibited I _SC across rabbit ciliary epithelium.The response to stromal cGMP was partly mediated by K⁺ channels at the stromal surface of the rabbit pigmented epithelial (PE) cells, since the effect was inhibited by stromal Ba²⁺, and was unaffected by Cl^– replacement, by bumetanide, or by DIDS. In contrast, the response to aqueous cGMP was not likely mediated by changing either K⁺ or Cl^– channels, based on transepithelial measurements of rabbit ciliary epithelium and complementary whole-cell patch clamping of cultured human nonpigmented ciliary epithelial (NPE) cells. The possibility of interacting effects between cGMP and cAMP in targeting the Na⁺,K⁺-exchange pump was also considered. Strophanthidin blocked the responses to either aqueous or stromal cGAMP. Applying 10 m forskolin to generate endogenous cAMP enhanced the subsequent response to aqueous cGMP by 80%.We conclude that cGMP has at least two actions on the ciliary epithelium. The major effect may be to reverse cAMP-mediated inhibition of the NPE Na⁺ pumps at the aqueous surface of both rabbit and cat ciliary epithelia. The second effect is likely mediated by increasing K⁺-channel and pump activity of the rabbit PE cells at the stromal surface.Supported in part by research grants from the National Institutes of Health EY10691 and EY00785 (for core facilities)] and from the American Health Assistance Foundation. We are grateful to Dr. Miguel Coca-Prados for graciously providing us with the ODM/SV40 NPE cells, and thank Prof. Rainer Greger (Albert-Ludwigs-Universitat, Freiburg, FRG) for kindly providing the NPPB.