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The potentiation and the desensitization and resensitization of B<jats:sub>2<\/jats:sub>receptor were assessed by measuring [<jats:sup>3<\/jats:sup>H]arachidonic acid release and [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>mobilization in Chinese hamster ovary cells transfected to express human ACE and B<jats:sub>2<\/jats:sub>receptor, or in endothelial cells with constitutively expressed ACE and receptor. Administration of bradykinin or its ACE-resistant analogue desensitized the receptor, but it was resensitized (arachidonic acid release or [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>mobilization) by agents such as enalaprilat (1 \u03bcmol\/L). Enalaprilat was inactive in the absence of ACE expression. La<jats:sup>3+<\/jats:sup>(100 \u03bcmol\/L) inhibited the apparent resensitization, probably by blocking the entry of extracellular calcium. Enalaprilat resensitized the receptor via ACE to release arachidonic acid by bradykinin at a lower concentration (5 nmol\/L) than required to mobilize [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>(1 \u03bcmol\/L). Monoclonal antibodies inhibiting the ACE N-domain active center and polyclonal antiserum potentiated bradykinin. The snake venom peptide BPP5a and metabolites of angiotensin and bradykinin (angiotensin-[1\u20139], angiotensin-[1\u20137], bradykinin-[1\u20138]; 1 \u03bcmol\/L) enhanced arachidonic acid release by bradykinin. Angiotensin-(1\u20139) and -(1\u20137) also resensitized the receptor. Enalaprilat potentiated the bradykinin effect in cells expressing a mutant ACE with a single N-domain active site. Agents that reacted with a single active site, on the N-domain or on the C-domain, potentiated bradykinin not by blocking its inactivation but by inducing crosstalk between ACE and the receptor. Enalaprilat enhanced signaling via ACE by G\u03b1<jats:sub>i<\/jats:sub>in lower concentration than by G\u03b1<jats:sub>q<\/jats:sub>-coupled receptor.<\/jats:p>","DOI":"10.1161\/01.hyp.33.3.835","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:53:46Z","timestamp":1339462426000},"page":"835-843","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":76,"title":["Enhancement of Bradykinin and Resensitization of Its B<sub>2<\/sub>Receptor"],"prefix":"10.1161","volume":"33","author":[{"given":"Branislav","family":"Marcic","sequence":"first","affiliation":[{"name":"From the Departments of Pharmacology (B.M., P.A.D., H.L.J., E.G.E.) and Anesthesiology (E.G.E.), University of Illinois College of Medicine at Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Deddish","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (B.M., P.A.D., H.L.J., E.G.E.) and Anesthesiology (E.G.E.), University of Illinois College of Medicine at Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert L.","family":"Jackman","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (B.M., P.A.D., H.L.J., E.G.E.) and Anesthesiology (E.G.E.), University of Illinois College of Medicine at Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ervin G.","family":"Erdo\u0308s","sequence":"additional","affiliation":[{"name":"From the Departments of Pharmacology (B.M., P.A.D., H.L.J., E.G.E.) and Anesthesiology (E.G.E.), University of Illinois College of Medicine at Chicago."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1080\/21548331.1993.11442827"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.23.6.813"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.3.258"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199209033271001"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199501123320203"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","unstructured":"Lewis EJ. 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