{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:20:25Z","timestamp":1791120025939,"version":"4.1.0"},"reference-count":28,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2000,12,1]]},"abstract":"<jats:p> We have studied G<jats:sub>q<\/jats:sub>-linked ANG II signaling [inositol phosphate (IP) accumulation, Ca<jats:sup>2+<\/jats:sup> mobilization] in primary cultures of rat cardiac fibroblasts (CFs) and have found that ANG II initiates a protein kinase C (PKC)-mediated negative feedback loop that rapidly terminates the ANG II response. Pharmacological inhibition of PKC by staurosporine and GF-109203X doubled IP production over that achieved in response to ANG II alone. Inhibition of PKC also led to larger Ca<jats:sup>2+<\/jats:sup> transients in response to ANG II, suggesting that Ca<jats:sup>2+<\/jats:sup> mobilization was proportional to G<jats:sub>q<\/jats:sub>-phospholipase C-IP<jats:sub>3<\/jats:sub> activity under the conditions studied. Depletion of cellular PKC by overnight treatment with phorbol 12-myristate 13-acetate (PMA) similarly augmented ANG II-induced IP production. Acute activation of PKC by PMA halved IP formation, with an EC<jats:sub>50<\/jats:sub>\u22481 nM; 4\u03b1-PMA was inactive. Time course data demonstrated that ANG II-mediated IP production fully desensitized within 30 s; PKC inhibition reduced the rate and extent of this desensitization. In cells desensitized to ANG II, a purinergic agonist still mobilized intracellular Ca<jats:sup>2+<\/jats:sup>, indicating that desensitization was homologous. The ANG II-induced Ca<jats:sup>2+<\/jats:sup> signal was fully resensitized within 30 min. The data demonstrate that a large portion of the IP-Ca<jats:sup>2+<\/jats:sup> responses of rat CFs to ANG II are short-lived because of rapid, PKC-mediated desensitization. <\/jats:p>","DOI":"10.1152\/ajpcell.2000.279.6.c1978","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T23:05:08Z","timestamp":1514156708000},"page":"C1978-C1985","source":"Crossref","is-referenced-by-count":15,"title":["Protein kinase C contributes to desensitization of ANG II signaling in adult rat cardiac fibroblasts"],"prefix":"10.1152","volume":"279","author":[{"given":"J. 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