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Abstract #11496 Published in IGR 6-3
Role of anions in nitric oxide-induced short-circuit current increase in isolated porcine ciliary processes
Wu R; Yao K; Flammer J; Haefliger IOInvestigative Ophthalmology and Visual Science 2004; 45: 3213-3222
PURPOSE: To investigate how nitric oxide (NO) modulates short-circuit current (Isc) in isolated porcine ciliary processes. METHODS: Isc changes (Ussing-type chamber) induced either by the NO donors SNP or SIN-1, or by the cGMP analogue 8-pCPT-cGMP were assessed. The effect of inhibitors of guanylate cyclase (10 μm ODQ, 100 μm LY83583), protein kinase G (30 μm Rp-8-pCPT-cGMP, 3 μm KT 5823), protein kinase A (1 μm KT 5720), or protein kinase C (1 μm Go6983) on SNP- or 8-pCPT-cGMP-induced Isc changes were investigated. The effect of inhibitors of anion channel (100 μm niflumic acid, 1 mM DIDS, and 1 mM 9-AC), K+-channel (10 mM TEA, 10 mM BaCl2), Na+-channel blockers (1 mM amiloride), Na+-K+-2Cl- cotransporter inhibitor (0.5 mM bumetanide), or carbonic anhydrase inhibitor (1 mM acetazolamide) was studied. In Cl-- or HCO3--free Krebs-Ringer solution, the effect of SNP- or 8-pCPT-cGMP-induced Isc changes was accessed. RESULTS: SNP, SIN-1, or 8-pCPT-cGMP increased Isc with a change in the potential difference that became more negative toward the nonpigmented epithelium (aqueous) side. The Isc increase induced by SNP or SIN-1, but not by 8-pCPT-cGMP, was prevented by ODQ and LY83583. SNP- and 8-pCPT-cGMP-induced Isc increases were prevented by Rp-8-pCPT-cGMP or KT5823 (but not by KT5720 or Go6983), or by niflumic acid, DIDS, 9-AC, or acetazolamide (but not by TEA, BaCl2, amiloride, or bumetanide). The effect of SNP and 8-pCPT-cGMP was abolished in Cl-- and reduced in HCO3--free solutions. CONCLUSIONS: NO activates a guanylate cyclase-cGMP-protein kinase G pathway that appears to stimulate stroma-to-aqueous anionic transport, possibly Cl-, in porcine ciliary epithelium.
Dr. R. Wu, Laboratory of Ocular Pharmacology and Physiology, University Eye Clinic Basel, Basel, Switzerland
Classification:
2.6.1 Production (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics)
3.6 Cellular biology (Part of: 3 Laboratory methods)