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We previously identified a peptidase that metabolizes Ang\u2010(1\u20107) to the inactive metabolite product Ang\u2010(1\u20104) in CSF of adult sheep. This study purified the peptidase 1445\u2010fold from sheep brain medulla and characterized this activity. The peptidase was sensitive to the chelating agents o\u2010phenanthroline and EDTA, as well as the mercury compound p\u2010chloromercuribenzoic acid (PCMB). Selective inhibitors to angiotensin\u2010converting enzyme, neprilysin, neurolysin, and thimet oligopeptidase did not attenuate activity; however, the metallopeptidase agent JMV\u2010390 was a potent inhibitor of Ang\u2010(1\u20107) hydrolysis (Ki\u00a0=\u00a00.8\u00a0nM). Kinetic studies using<jats:sup>125<\/jats:sup>I\u2010labeled Ang\u2010(1\u20107), Ang II, and Ang I revealed comparable apparent<jats:italic>K<\/jats:italic><jats:sub>m<\/jats:sub>values (2.6, 2.8, and 4.3\u00a0\u03bcM, respectively), but a higher apparent<jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub>for Ang\u2010(1\u20107) (72 vs. 30 and 6\u00a0nmol\/min\/mg, respectively;<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.01). HPLC analysis of the activity confirmed the processing of unlabeled Ang\u2010(1\u20107) to Ang\u2010(1\u20104) by the peptidase, but revealed &lt;\u00a05% hydrolysis of Ang II or Ang I, and no hydrolysis of neurotensin, bradykinin or apelin\u201013. The unique characteristics of the purified neuropeptidase may portend a novel pathway to influence actions of Ang\u2010(1\u20107) within the brain.<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12720-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><jats:p>Angiotensin\u2010(1\u20107) actions are mediated by the AT<jats:sub>7<\/jats:sub>\/Mas receptor and include reduced blood pressure, decreased oxidative stress, enhanced baroreflex sensitivity, and increased nitric oxide (NO). Ang\u2010(1\u20107) is directly formed from Ang I by neprilysin (NEP). We identify a new pathway for Ang\u2010(1\u20107) metabolism in the brain distinct from angiotensin\u2010converting enzyme\u2010dependent hydrolysis. The Ang\u2010(1\u20107) endopeptidase (A7\u2010EP) degrades the peptide to Ang\u2010(1\u20104) and may influence central Ang\u2010(1\u20107) tone.<\/jats:p>","DOI":"10.1111\/jnc.12720","type":"journal-article","created":{"date-parts":[[2014,3,25]],"date-time":"2014-03-25T06:58:41Z","timestamp":1395730721000},"page":"313-323","source":"Crossref","is-referenced-by-count":17,"title":["Evidence for an angiotensin\u2010(1\u20107) neuropeptidase expressed in the brain medulla and<scp>CSF<\/scp>of sheep"],"prefix":"10.1111","volume":"130","author":[{"given":"Allyson C.","family":"Marshall","sequence":"first","affiliation":[{"name":"Hypertension and Vascular Research Center Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy T.","family":"Pirro","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra I.","family":"Diz","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Chappell","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center Wake Forest School of Medicine Winston Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1987.tb13160.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.2000.279.5.F841"},{"key":"e_1_2_7_4_1","article-title":"Nuclear expression of components of renin\u2010angiotensin system in the NRK52E cells","author":"Alzayadneh E. 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