{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T22:45:42Z","timestamp":1759099542362},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,5,15]]},"abstract":"<jats:p>Atrionatriuretic peptide (ANP) lowers intraocular pressure in the eyes of humans and rabbits. We examined the effects of natriuretic peptides on cGMP formation and 125I-labelled-ANP binding to cultured cells derived from ciliary body epithelium, the site of aqueous humour formation in the eye. ANP, brain natriuretic peptide (BNP) and C-natriuretic peptide (CNP) at 1 \u03bcM stimulated cGMP formation 8.2(\u00b11.2)-fold, 4.8(\u00b10.6)-fold and 87.3(\u00b112.1)-fold respectively. 125I-ANP bound to intact cells at a single site, with a dissociation constant KD = 0.30\u00b10.01 nM. BNP was as effective as ANP in displacing 125I-ANP, whereas CNP displaced label with a slightly higher IC50. 125I-ANP binding was displaced &amp;gt; 95% by c-ANP, a specific ligand for natriuretic peptide C receptors (NPR-C). Cross-linking of 125I-ANP to cells labelled predominantly a protein of Mr 62000. These data suggest that 125I-ANP binding was primarily to NPR-C, whereas cGMP stimulation occurred primarily via natriuretic peptide B receptors (NPR-B). Vasopressin and histamine, both activators of the inositol phosphate\/diacylglycerol phosphate pathway in non-pigmented ciliary epithelial cells, inhibited CNP stimulation of guanylate cyclase (NPR-B) and 125I-ANP binding (NPR-C) by 30\u201338%. Inhibition was mimicked by PMA, dioctanoylglycerol and phorbol didecanoate, whereas 4\u03b1 phorbol didecanoate had no effect. Staurosporine and bisindolylmaleimide both blocked inhibition of 125I-ANP binding and cGMP formation by PMA. These results suggest that protein kinase C (PKC) down-regulates both NPR-B and NPR-C. PKC down-regulation of NPR-B varied inversely with CNP concentration. Inhibition by 1 \u03bcM PMA was 30.6(\u00b14.0)% with 500 nM CNP, but 83.4(\u00b18.8)% with 10 nM CNP, indicating that increasing CNP could partially overcome inhibition by PMA. Since extracellular CNP levels were not affected by PKC activation, the effect of PKC on NPR-B is best explained as a reduction in NPR-B affinity for CNP. NPR-C measured as 125I-ANP binding was likewise reduced 36.4(\u00b15.1)% by exposure to PMA. In contrast with NPR-B inhibition, however, inhibition of NPR-C was due largely to a reduction in the number of receptor binding sites per cell rather than a reduction in receptor affinity for ligand. The data therefore suggest that both NPR-B and NPR-C are down-regulated by PKC, but that the mechanisms of down-regulation of the two receptors are different.<\/jats:p>","DOI":"10.1042\/bj3240049","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:54:41Z","timestamp":1439243681000},"page":"49-55","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Differential regulation of natriuretic peptide receptors on ciliary body epithelial cells"],"prefix":"10.1042","volume":"324","author":[{"given":"Richard B.","family":"CROOK","sequence":"first","affiliation":[{"name":"Beckman Vision Center, Department of Ophthalmology, Box 0730, University of California, San Francisco, San Francisco, CA 94143, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan T.","family":"CHANG","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/324\/1\/49\/625243\/bj3240049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/324\/1\/49\/625243\/bj3240049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:24:00Z","timestamp":1637713440000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/324\/1\/49\/33341\/Differential-regulation-of-natriuretic-peptide"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,5,15]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1997,5,15]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3240049","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,5,15]]}}}