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ENDOCRINE AND REPRODUCTIVE

Bremazocine Increases C-Type Natriuretic Peptide Levels in Aqueous Humor and Enhances Outflow Facility

Storm Eye Institute, Department of Ophthalmology, Medical University of South Carolina, Charleston, South Carolina (D.E.P., M.M.); and Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia (K.R.M.R.)

A relatively selective agonist of opioid receptors (KOR), bremazocine (BRE), lowers intraocular pressure in rabbits, in part, by increasing natriuretic peptide levels in aqueous humor and by enhancing total outflow facility (TOF). Natriuretic peptide (NP) levels [atrial NP (ANP), brain NP (BNP), and C-type NP (CNP)] were measured in aqueous humor of rabbits either by radioimmunoassay or enzyme immunoassay. TOF was determined in rabbits by two-level constant pressure perfusion of the anterior chamber. Experimental regimens included topical treatment with BRE in the presence or absence of KOR antagonist (norbinaltorphimine), protein kinase C inhibitor (chelerythrine), and natriuretic peptide receptor antagonist (isatin). The rank order of basal NP levels in aqueous humor of rabbits was BNP CNP > ANP. Topical administration of BRE (1–100 µg) caused dose-related elevations of CNP levels in aqueous humor that were inhibited by topical pretreatment with either norbinaltorphimine (100 µg, bilaterally) or chelerythrine (10 µg, bilaterally). Topically administered BRE (100 µg) also elevated levels of ANP and BNP in aqueous humor and evoked an 80% increase in TOF. The increase in TOF was antagonized by topical pretreatment with either norbinaltorphimine (100 µg, bilaterally) or isatin (100 µg, bilaterally). Bremazocine induced an increase in NP (ANP, BNP, and CNP) levels and TOF in rabbits by activating KOR. The increase in CNP levels elicited by BRE was inhibited by norbinaltorphimine and chelerythrine; therefore, this event is most likely mediated by a KOR-linked activation of protein kinase C. These data provide evidence that the increase in TOF elicited by BRE was mediated by a KOR-activated paracrine effect of NPs on tissues within ocular outflow tract(s).

Address correspondence to: Dr. David E. Potter, Professor of Ophthalmology, Medical University of South Carolina, Storm Eye Institute, Room 518, 167 Ashley Avenue, Charleston, SC 29425. E-mail: potterde{at}musc.edu