{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:30:27Z","timestamp":1770741027929,"version":"3.49.0"},"reference-count":30,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1997,11,1]]},"abstract":"<jats:p> A role for protein kinase C (PKC)-\u03b4 and -\u03b6 isotypes in \u03b1<jats:sub>1<\/jats:sub>-adrenergic regulation of human tracheal epithelial Na-K-2Cl cotransport was studied with the use of isotype-specific PKC inhibitors and antisense oligodeoxynucleotides to PKC-\u03b4 or -\u03b6 mRNA. Rottlerin, a PKC-\u03b4 inhibitor, blocked 72% of basolateral-to-apical, bumetanide-sensitive<jats:sup>36<\/jats:sup>Cl flux in nystatin-permeabilized cell monolayers stimulated with methoxamine, an \u03b1<jats:sub>1<\/jats:sub>-adrenergic agonist, with a 50% inhibitory concentration of 2.3 \u03bcM. Methoxamine increased PKC activity in cytosol and a particulate fraction; the response was insensitive to PKC-\u03b1 and -\u03b2<jats:sub>II<\/jats:sub>isotype-specific inhibitors, but was blocked by general PKC inhibitors and rottlerin. Rottlerin also inhibited methoxamine-induced PKC activity in immune complexes of PKC-\u03b4, but not PKC-\u03b6. At the subcellular level, methoxamine selectively elevated cytosolic PKC-\u03b4 activity and particulate PKC-\u03b6 activity. Pretreatment of cell monolayers with antisense oligodeoxynucleotide to PKC-\u03b4 for 48 h reduced the amount of whole cell and cytosolic PKC-\u03b4, diminished whole cell and cytosolic PKC-\u03b4 activity, and blocked methoxamine-stimulated Na-K-2Cl cotransport. Sense oligodeoxynucleotide to PKC-\u03b4 and antisense oligodeoxynucleotide to PKC-\u03b6 did not alter methoxamine-induced cotransport activity. These results demonstrate the selective activation of Na-K-2Cl cotransport by cytosolic PKC-\u03b4. <\/jats:p>","DOI":"10.1152\/ajpcell.1997.273.5.c1632","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T17:14:53Z","timestamp":1514135693000},"page":"C1632-C1640","source":"Crossref","is-referenced-by-count":30,"title":["Antisense oligodeoxynucleotide to PKC-\u03b4 blocks  \u03b1<sub>1<\/sub>-adrenergic activation of Na-K-2Cl cotransport"],"prefix":"10.1152","volume":"273","author":[{"given":"Carole M.","family":"Liedtke","sequence":"first","affiliation":[{"name":"The Cystic Fibrosis Center and Departments of Pediatrics and of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Cole","sequence":"additional","affiliation":[{"name":"The Cystic Fibrosis Center and Departments of Pediatrics and of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)34089-9"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)49576-8"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)53959-4"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1996.0236"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1990.258.2.C227"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)82127-5"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117978"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1042\/bj2880319"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50291-5"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1994.1199"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1994.266.5.C1440"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.8.2.963"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1992.262.1.C15"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(96)00079-3"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/13.11.1997"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1993.tb18179.x"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1993.tb05850.x"},{"issue":"6","key":"B18","first-page":"L183","volume":"262","author":"Liedtke C. 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