{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:38:38Z","timestamp":1790948318010,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To investigate the effects of capsaicinoids on airway anion transporters, we recorded and analyzed transepithelial currents in human airway epithelial Calu-3 cells. Application of capsaicin (100 \u03bcM) attenuated vectorial anion transport, estimated as short-circuit currents (ISC), before and after stimulation by forskolin (10 \u03bcM) with concomitant reduction of cytosolic cyclic AMP (cAMP) levels. The capsaicin-induced inhibition of ISC was also observed in the response to 8-bromo-cAMP (1 mM, a cell-permeable cAMP analog) and 3-isobutyl-1-methylxanthine (1 mM, an inhibitor of phosphodiesterases). The capsaicin-induced inhibition of ISC was attributed to suppression of bumetanide (an inhibitor of the basolateral Na+-K+-2 Cl\u2212 cotransporter 1)- and 4,4\u2032-dinitrostilbene-2,2\u2032-disulfonic acid (an inhibitor of basolateral HCO3\u2212-dependent anion transporters)\u2013sensitive components, which reflect anion uptake via basolateral cAMP-dependent anion transporters. In contrast, capsaicin potentiated apical Cl\u2212 conductance, which reflects conductivity through the cystic fibrosis transmembrane conductance regulator, a cAMP-regulated Cl\u2212 channel. All these paradoxical effects of capsaicin were mimicked by capsazepine. Forskolin application also increased phosphorylated myosin phosphatase target subunit 1, and the phosphorylation was prevented by capsaicin and capsazepine, suggesting that these capsaicinoids assume aspects of Rho kinase inhibitors. We also found that the increments in apical Cl\u2212 conductance were caused by conventional Rho kinase inhibitors, Y-27632 (20 \u03bcM) and HA-1077 (20 \u03bcM), with selective inhibition of basolateral Na+-K+-2 Cl\u2212 cotransporter 1. Collectively, capsaicinoids inhibit cAMP-mediated anion transport through down-regulation of basolateral anion uptake, paradoxically accompanied by up-regulation of apical cystic fibrosis transmembrane conductance regulator\u2013mediated anion conductance. The latter is mediated by inhibition of Rho-kinase, which is believed to interact with actin cytoskeleton.<\/jats:p>","DOI":"10.1165\/rcmb.2010-0332oc","type":"journal-article","created":{"date-parts":[[2011,1,28]],"date-time":"2011-01-28T21:20:27Z","timestamp":1296249627000},"page":"684-691","source":"Crossref","is-referenced-by-count":7,"title":["Capsaicinoids Regulate Airway Anion Transporters through Rho Kinase\u2013 and Cyclic AMP\u2013Dependent Mechanisms"],"prefix":"10.1093","volume":"45","author":[{"given":"Yoshitaka","family":"Hibino","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Morise","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, 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