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cGMP modulates transport across the ciliary epithelium

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Abstract

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 μm 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.

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Authors and Affiliations

  1. Department of Physiology, University of Pennsylvania, School of Medicine, 19104-6085, Philadelphia, PA

    D. A. Carré & M. M. Civan

  2. Department of Medicine, University of Pennsylvania, School of Medicine, 19104-6085, Philadelphia, PA

    M. M. Civan

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  1. D. A. Carré
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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.

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Carré, D.A., Civan, M.M. cGMP modulates transport across the ciliary epithelium. J. Membarin Biol. 146, 293–305 (1995). https://doi.org/10.1007/BF00233949

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