{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T01:58:09Z","timestamp":1774663089456,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":4936,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1991,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have demonstrated previously that a variety of agents including corticosteroids, thyroid hormone, cationophores, methylxanthines, and analogues of cAMP\u2013all of which have diversified functions in various tissues\u2013elevate cellular angiotensin converting enzyme (ACE) activity of bovine endothelial cells in culture. In addition to these agents, we have now found that direct and receptor\u2010mediated stimulators of adenylate cyclase, i.e., forskolin and cholera toxin, increase cellular ACE activity after 48 h incubation in culture. In an attempt to search out a more unifying concept of these stimulatory effects, we have further investigated the roles of second messengers in the stimulatory actions. Ca<jats:sup>2+<\/jats:sup> ionophore, A23187 produced significant increases in both intracellular Ca<jats:sup>2+<\/jats:sup> and ACE of endothelial cells. In contrast to Ca<jats:sup>2+<\/jats:sup> ionophore, agents that transiently mobilize Ca<jats:sup>2+<\/jats:sup> from intracellular reserves such as bradykinin, acetylcholine, and ATP have no effect on the level of cellular ACE. Representative agents that elevate cellular cAMP (e.g., isobutyl methylxanthine [IBMX] and dibutyryl cAMP) elevated cellular ACE, but the slightly increased [Ca<jats:sup>2+<\/jats:sup>], produced by these agents did not reach statistical significance. While IBMX, cholera toxin, and forskolin elevated cellular cAMP, other ACE stimulatory agents (hormones and cationophores) had no effect on cAMP. Ca<jats:sup>2+<\/jats:sup> ionophore and the agents that elevated intracellular cAMP potentiated the effect of dexamethasone, thyroid hormone, and aldosterone in elevating cellular ACE activity. Increases in ACE activity produced by all stimulants were inhibited by the presence of 10\u201350 nM ouabain in the culture medium. Inhibition of ACE elevation by ouabain was reversed by increasing the extracellular [K<jats:sup>+<\/jats:sup>], thereby implicating Na<jats:sup>+<\/jats:sup>, K<jats:sup>+<\/jats:sup>\u2010ATPase in the ACE regulatory mechanism. These results support the presence of multiple independent mechanisms for the regulation of cellular ACE. In addition to possible involvement of intracellular Ca<jats:sup>2+<\/jats:sup>\u2010 and cAMP\u2010dependent pathways, ACE is also increased by corticosteroids and thyroid hormone through mechanisms unrelated to Ca<jats:sup>2+<\/jats:sup>\u2010and cAMP.<\/jats:p>","DOI":"10.1002\/jcp.1041480220","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T08:17:57Z","timestamp":1109405877000},"page":"327-335","source":"Crossref","is-referenced-by-count":10,"title":["Involvement of second messenger systems in stimulation of angiotensin converting enzyme of bovine endothelial cells"],"prefix":"10.1002","volume":"148","author":[{"given":"Yamuna","family":"Dasarathy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry L.","family":"Fanburg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2697(76)80064-4"},{"key":"e_1_2_1_3_1","first-page":"353","volume-title":"The Na+\/K+\u2010Pump, Part B: Cellular Aspects","author":"Bertorello A.","year":"1988"},{"key":"e_1_2_1_4_1","first-page":"F57","article-title":"Regulation of Na+\u2010K+\u2010ATPase activity in kidney proximal tubules: involvement of GTP binding proteins","volume":"256","author":"Bertorello A.","year":"1989","journal-title":"Am. 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