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Abstract #13110 Published in IGR 7-3
Effects of unoprostone and endothelin 1 on L-type channel currents in human trabecular meshwork cells
Thieme H; Steinhausen K; Ottlecz A; Lambrou GN; Strauss O; Wiederholt M; Rosenthal ROphthalmic Research 2005; 37: 293-300
BACKGROUND: The trabecular meshwork (TM) is a smooth muscle-like tissue with contractile properties and by this mechanisms involved in the regulation of aqueous humor outflow. Isopropyl unoprostone (Rescula, Novartis Ophthalmics), a synthetic docosanoid, reduces intraocular pressure in glaucoma patients and normal subjects. In isolated TM strips, unoprostone reduces TM contractility in the presence of endothelin 1 (ET-1). However, the signal transduction pathway of unoprostone still remains unclear. Since L-type channel currents are known to influence the contractility of TM, we examined the effects of unoprostone and ET-1 on L-type channel currents of TM cells. METHODS: The effects of unoprostone, ET-1 and the tyrosine kinase inhibitor herbimycin A on L-type channel currents of cultured human TM cells were investigated using the perforated patch configuration of the patch-clamp technique. RESULTS: Application of ET-1 had no effect on L-type channel currents. Unoprostone led to a dose-dependent reduction of control currents. The effect of unoprostone is independent of ET-1. After preincubation of cells with herbimycin A, unoprostone had no effect on the L-type channel current amplitude. Human TM cells preincubated with herbimycin A showed a reduced current density compared with control cells. Both substances, unoprostone and herbimycin A, increased the inactivation time constant of L-type channel currents. CONCLUSION: We conclude that unoprostone reduces the activity of L-type Ca2+ channels. This effect seems to be independent of ET-1. The signal transduction pathway seems to be mediated by tyrosine kinases.
Dr. H. Thieme, Augenklinik und Hochschulambulanz, Berlin, Germany
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)
