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Abstract #13006 Published in IGR 7-3
The cross-species A3 adenosine-receptor antagonist MRS 1292 inhibits adenosine-triggered human nonpigmented ciliary epithelial cell fluid release and reduces mouse intraocular pressure
Yang H; Avila MY; Peterson-Yantorno K; Coca-Prados M; Stone RA; Jacobson KA; Civan MMCurrent Eye Research 2005; 30: 747-754
PURPOSE: Antagonists to A3 adenosine receptors (ARs) lower mouse intraocular pressure (IOP), but extension to humans is limited by species variability. We tested whether the specific A3 AR antagonist MRS 1292, designed to cross species, mimicks the effects of other A3 AR antagonists on cultured human nonpigmented ciliary epithelial (NPE) cells and mouse IOP. METHODS: NPE cell volume was monitored by electronic cell sorting. Mouse IOP was measured with the Servo-Null Micropipette System. RESULTS: Adenosine triggered A3 AR-mediated shrinkage of human NPE cells. Shrinkage was blocked by MRS 1292 (IC50 = 42 ± 11 nM, p < 0.01) and by another A3 AR antagonist effective in this system, MRS 1191. Topical application of the A3 AR agonist IB-MECA increased mouse IOP. MRS 1292 reduced IOP by 4.0 ± 0.8 mmHg at 25-μM droplet concentration (n = 10, p < 0.005). CONCLUSIONS: MRS 1292 inhibits A3AR-mediated shrinkage of human NPE cells and reduces mouse IOP, consistent with its putative action as a cross-species A3 antagonist.
Dr. H. Yang, Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6085, USA
Classification:
11.4 Prostaglandins (Part of: 11 Medical treatment)