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Intraocular pressure (IOP) lowering effects of 2 kinins were also investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Previously documented procedures were utilized throughout these studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Kinninogen mRNA was most abundant in TM, ciliary body (CB), and optic nerve head and appeared elevated in glaucomatous h-TM tissue. High levels of B\n                      <jats:sub>2<\/jats:sub>\n                      -receptor mRNA were found in the sclera, iris, TM, and CB. B\n                      <jats:sub>2<\/jats:sub>\n                      -receptor subtype protein was localized in cells of the monkey and h-TM, and the treatment of isolated h-TM cells with transforming growth factor-\u03b22 (5\u2009ng\/mL) caused significant (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.04) downregulation of B\n                      <jats:sub>2<\/jats:sub>\n                      -receptor mRNA. In isolated primary h-TM cells, BK (EC\n                      <jats:sub>50<\/jats:sub>\n                      =0.8\u00b10.2\u2009nM;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      =19) and Met-Lys-BK (EC\n                      <jats:sub>50<\/jats:sub>\n                      =6.5\u00b11.5\u2009nM) mobilized intracellular Ca\n                      <jats:sup>2+<\/jats:sup>\n                      and induced the release of prostaglandins (PGs) that was blocked by 2 B\n                      <jats:sub>2<\/jats:sub>\n                      -receptor antagonists [HOE-140; (S)-WIN-64338]. The cyclooxygenase inhibitor, bromfenac, abolished BK-induced PGs production. BK concentration dependently increased cell impedance, and it significantly (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05) decreased h-TM cell volume\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      . Intravitreal (ivt) administration of BK (50\u2009\u03bcg), but not a B\n                      <jats:sub>1<\/jats:sub>\n                      -agonist (Sar-[D-Phe\n                      <jats:sup>9<\/jats:sup>\n                      ]-Des-Arg\n                      <jats:sup>9<\/jats:sup>\n                      -BK; also at 50\u2009\u03bcg), efficaciously lowered IOP (22.9% to 37% from baseline) of Dutch-Belted rabbits that naturally have high IOPs (27\u201328\u2009mmHg).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      BK activates multiple signal transduction pathways in h-TM cells via B\n                      <jats:sub>2<\/jats:sub>\n                      -receptors that also mediate IOP reduction as observed in rabbits following ivt administration of BK. These ocular hypotensive effects of BK may be physiologically important and suggest a novel therapeutic potential of BK-related B\n                      <jats:sub>2<\/jats:sub>\n                      -agonists.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/jop.2013.0105","type":"journal-article","created":{"date-parts":[[2013,11,16]],"date-time":"2013-11-16T10:22:45Z","timestamp":1384597365000},"page":"21-34","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Trabecular Meshwork Bradykinin Receptors: mRNA Levels, Immunohistochemical Visualization, Signaling Processes Pharmacology, and Linkage to IOP Reduction"],"prefix":"10.1177","volume":"30","author":[{"given":"Najam A.","family":"Sharif","sequence":"first","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parvaneh","family":"Katoli","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis R.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linya","family":"Li","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouxi","family":"Xu","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Klekar","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Earnest","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenouda","family":"Yacoub","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwenette","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasreen","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan R.","family":"Shepard","sequence":"additional","affiliation":[{"name":"Pharmaceutical Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorette","family":"Ellis","sequence":"additional","affiliation":[{"name":"University of North Texas Systems College of Pharmacy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,11,16]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01945357"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-5155(99)00024-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1159\/000267273"},{"key":"e_1_3_2_5_2","first-page":"1241","article-title":"NPR-B natriuretic peptide receptors in human corneal epithelium: mRNA, immunohistochemistochemical, protein and biochemical pharmacology studies","volume":"16","author":"Katoli P.","year":"2010","unstructured":"Katoli P., , Sharif N.A., , Sule A., , and Dimitrijevich S.D. 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