Functional expression of components of the natriuretic peptide system in human ocular nonpigmented ciliary epithelial cells

The expression of the natriuretic peptide system in the human ocular ciliar y epithelium (CE) and in cultured nonpigmented (NPE) ciliary epithelial cel ls was examined. By RT-PCR and DNA sequencing, we demonstrated that the CE and NPE cells express mRNA for (i) ANP; (ii) BNP; (iii) NPR-A, NPR-B, and N PR-C receptors; and (iv) the neutral endopeptidase 24.11. Radioimmunoassay results indicate that BNP is secreted by cultured NPE cells at much higher levels than ANP. NPR-A and NPR-B receptors elicited a cGMP response to ANP, BNP, and CNP, in a rank order of potency (CNP much greater than ANP greate r than or equal to BNP), indicative that the NPR-B receptor is predominant in NPE cells. A71915, an inhibitor of NPR-A activity, attenuated (65-75%) c GMP response to ANP and BNP, but not to CNP. C-ANP(4-23) elicited an inhibi tory effect (30-37%) on basal levels of cAMP in NPE cells and on forskolin NPE-treated cells, indicative that the NPR-C receptor is functional in thes e cells. PMA induced, in NPE cells, a long-term down-regulation (75-85%) of NPR-C receptor mRNA, but not of NPR-A or NPR-B receptor mRNA, suggesting a differential regulation of NPR-C receptor mRNA via activation of PKC. Coll ectively, our data provide molecular evidence that all the components of th e natriuretic peptide system with the exception of CNP are coexpressed in t he ocular NPE ciliary epithelial cells, where they may function as local au tocrine/paracrine modulators to influence eye pressure. (C) 1999 Academic P ress.