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Chi-Wai Do, Chi-Wing Kong, Chi-Ho To; cAMP Inhibits Transepithelial Chloride Secretion across Bovine Ciliary Body/Epithelium. Invest. Ophthalmol. Vis. Sci. 2004;45(10):3638-3643. doi: 10.1167/iovs.03-1343.
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purpose. To investigate the potential significance of cAMP in the regulation of Cl− transport across the bovine ciliary body/epithelium (CBE).
methods. Fresh native bovine CBE preparation was mounted in a modified Ussing chamber. The effects of cAMP-stimulating agents on short-circuit current (Isc) and net 36Cl− secretion were determined.
results. Addition of cAMP-stimulating agents inhibited net Cl− secretion. Forskolin, when added bilaterally, reduced Cl− secretion by 60%. Similarly, bilateral isoproterenol or vasoactive intestinal peptide inhibited Cl− transport by 15% and 37%, respectively, suggesting a cAMP-sensitive Cl− transport across the ciliary epithelium. This notion was supported by the exogenous application of 8-bromo-cAMP (8-Br-cAMP) or 3-isobutyl-1-methylxanthine (IBMX), which reduced the net Cl− secretion by 49% and 85%, respectively. In unstimulated preparations, addition of 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) to the blood side had no effects on Isc and net Cl− transport, indicating that Cl− reabsorption was negligible under baseline conditions. Also, pretreatment with NPPB from the blood side did not prevent forskolin-induced Isc inhibition, suggesting that the inhibition of Cl− transport did not result from the facilitation of Cl− reabsorption. However, pretreatment with heptanol from both sides completely blocked the forskolin-induced Isc inhibition, suggesting that cAMP may reduce Cl− transport by uncoupling the intercellular gap junctions.
conclusions. The results suggest that cAMP plays a crucial role in modulating Cl− secretion across the ciliary epithelium. The effect is possibly mediated, at least in part, by the regulation of the permeability of gap junctions between pigmented and nonpigmented ciliary epithelial cells.
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