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K.R. Russell, D.E. Potter; Secretion of Natriuretic Peptides into the Aqueous Humor: Regulation by Kappa-Opioid Receptors . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3427.
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Purpose: To compare basal and stimulated natriuretic peptide (NP) levels in the aqueous humor of the rabbit and to determine the mechanism(s) by which bremazocine (BRE), a kappa-opioid receptor agonist, stimulates the secretion of these peptides. Methods: Aqueous humor was removed by paracentesis from dark-adapted New Zealand white (NZW) rabbits in basal and BRE-stimulated states and the levels of the natriuretic peptides (ANP, CNP and BNP) determined by either radioimmunoassay (ANP and CNP) or enzymeimmunoassay (BNP). In separate experiments, rabbit eyes were treated topically and bilaterally with BRE (1, 10 and 100 µg) to determine effects on NP levels. At 0.5hr post BRE, the rabbits were sacrificed and the aqueous humor removed. In other experiments, eyes were pretreated topically with either the kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI) or the protein kinase C (PKC) inhibitor, chelerythrine chloride (CHLR), 0.5hr before the challenge with BRE. Results: In the basal state, BNP was present in the highest concentration (448pg/mL). By comparison, the levels of ANP and CNP were 7 and 29 pg/mL, respectively. BRE caused dose-related increases in NP levels, which was antagonized by pre-treatment with nor-BNI (ANP and CNP). The increase in aqueous CNP levels evoked by BRE was attenuated by prior treatment with CHLR. Conclusion: These data demonstrate that the NPs (ANP, BNP and CNP) are secreted into the aqueous humor of rabbits in the basal state and that their levels can be augmented by BRE in a dose-related manner. Since the kappa-opioid receptor agonist, BRE, has been shown to reduce intraocular pressure, increases in NP levels could be responsible, in part, for BRE-induced reductions in IOP. Based on the antagonism by nor-BNI, these BRE-induced changes in NP levels are presumed to be due to actions at kappa-opioid receptors in the ciliary epithelium. The attenuation of the BRE-induced elevation of CNP levels by CHLR also suggests a role for PKC-dependent activity in BRE-evoked augmentation of NP levels in aqueous humor. CR: None Support:EY12807
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