Dynorphin Modulates Ocular Hydrodynamics and Releases Atrial Natriuretic Peptide via Activation of κ-Opioid Receptors

Abstract

The present study was designed to investigate the effect of the kappa opioid receptor (KOR) agonist, dynorphin A (Dyn), on aqueous humor dynamics (intraocular pressure (IOP), aqueous humor flow rate (AFR)), pupil diameter (PD) and atrial natriuretic peptide (ANP) levels in the aqueous humor of the rabbit. Topical and unilateral application of Dyn caused dose-related, bilateral reductions in IOP and AFR. An intermediate dose of Dyn (33 μg) caused bilateral mydriasis whereas a higher dose (100 μg) caused unilateral miosis. The Dyn-induced reduction in IOP and aqueous flow rate as well as the mydriasis were antagonized by nor-binaltorphimine (nor-BNI), a relatively selective KOR antagonist. In addition to the effects on IOP, PD and AFR, Dyn caused dose-related increases in aqueous ANP levels that was attenuated by nor-BNI. The present study indicates that Dyn reduces IOP, in part, by reducing AFR. Moreover, the increase in ANP levels could be involved in the Dyn-induced reductions in IOP and AFR. Based upon the inhibitory effects of nor-BNI, these Dyn-induced events are due, in part, to the activation of KORs in the ciliary processes of the eye.