{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T19:35:49Z","timestamp":1778614549481,"version":"3.51.4"},"reference-count":42,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[1998,6,1]],"date-time":"1998-06-01T00:00:00Z","timestamp":896659200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The mechanism of action of synthetic CCRF-DP, the corticotropin-releasing factor (CRF)-related diuretic peptide of the salt marsh mosquito Culex salinarius, was investigated in isolated Malpighian tubules of the yellow fever mosquito Aedes aegypti. A low concentration of CCRF-DP (10\u22129 mol l\u22121) caused a small but insignificant increase in transepithelial secretion of NaCl and fluid, but significantly reduced transepithelial voltage and resistance without a change in short-circuit current, pointing to the stimulation of passive Cl\u2212 transport through the paracellular pathway as the principal mechanism of a mild diuresis. Significant changes in voltage and resistance but not in short-circuit current were duplicated by the ionophore A23187 (0.4 \u03bcmol l\u22121), suggesting Ca2+ as a second messenger at 10\u22129 mol l\u22121 CCRF-DP. A high concentration of CCRF-DP (10\u22127 mol l\u22121) significantly increased transepithelial secretion of NaCl and fluid and significantly increased short-circuit current, pointing to the stimulation of active Na+ transport through the transcellular pathway as the mechanism of a strong diuresis. This effect was mimicked by dibutyryl-cAMP, suggesting cAMP as a second messenger at 10\u22127 mol l\u22121 CCRF-DP. Dibutyryl-cGMP had no effects. These results suggest dose-dependent, receptor-mediated effects of CCRF-DP that target discrete transport pathways via discrete second messengers: low concentrations of CCRF-DP cause a mild diuresis, apparently via Ca2+-mediated effects on paracellular Cl\u2212 transport, and high concentrations cause a strong diuresis via cAMP-mediated effects on active transcellular Na+ transport in addition to the effects on the paracellular pathway.<\/jats:p>","DOI":"10.1242\/jeb.201.11.1753","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T23:28:06Z","timestamp":1619220486000},"page":"1753-1762","source":"Crossref","is-referenced-by-count":51,"title":["The Concentration-Dependence of Crf-Like Diuretic Peptide: Mechanisms of Action"],"prefix":"10.1242","volume":"201","author":[{"given":"Thomas M.","family":"Clark","sequence":"first","affiliation":[{"name":"Washington State University 1 Department of Zoology , , Pullman, WA 99164, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy K.","family":"Hayes","sequence":"additional","affiliation":[{"name":"2 Bayer Corporation, 1017 Main Campus Drive, Suite 3800, Raleigh, NC 27606, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. 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