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K Russell, DE Potter; Dynorphin A and ocular hydrodynamics . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1973.
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The endogenous kappa opioid receptor agonist, Dynorphin A (Dyn) has been shown to reduce intraocular pressure but the mechanism by which it brings about this reduction has not been determined. Purpose:To investigate the effect of Dyn on aqueous humor flow rate (AFR) and atrial natriuretic peptide (ANP) levels. Methods:Aqueous flow rates were determined using a fluorophotometric technique utilizing 2% fluorescein. Following unilateral, topical treatment with Dyn (10, 33 and 100 µg/25µL) to normal, dark-adapted New Zealand white (NZW) rabbits, flow rates were determined at 0.5, 1.5, 2.5, 3.5 and 4.5hr post drug. The antagonistic effect of the relatively selective kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI, 100µg/25µL) on Dyn-induced changes in AFR was determined in separate experiments. In other experiments, rabbit eyes were treated topically with Dyn (1, 10 and 100 µg) to determine if changes in ANP levels occurred. At 0.5hr post drug, the rabbits were sacrificed and the aqueous humor removed by paracentesis. The concentration of ANP in the aqueous samples was determined by a radioimmunoassay (RIA) technique. Subsequently, eyes were pretreated with nor-binaltorphimine (nor-BNI, 10µM), 0.5hr before the challenge with Dyn (2.5mM). Results:Dyn caused a dose-related, significant reduction in AFR at 0.5hr post drug and this reduction was maintained for approximately 4hr. The reduction in AFR was antagonized by pre-treatment with nor-BNI. Dyn caused a dose-related increase in aqueous ANP levels which was attenuated by prior treatment with nor-BNI. Conclusion:These data demonstrate that Dyn reduces IOP, in part, by reducing aqueous flow rate. Moreover, the increase in ANP levels could be involved in the Dyn-induced reductions in AFR. Based on the antagonism by nor-BNI, these Dyn-induced events are due, in part, to actions at kappa opioid receptors in the ciliary processes
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