{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T00:38:12Z","timestamp":1772930292122,"version":"3.50.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2000,3,1]],"date-time":"2000-03-01T00:00:00Z","timestamp":951868800000},"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":[[2000,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We compared the action of methacholine (MCh) and uridine 5\u2032-triphosphate (UTP) with and without pretreatment with the chloride channel blocker 4,4\u2032-diisothiocyano-2,2\u2032-stilbenedisulfonate (DIDS) on the transepithelial potential difference (PD), the mucus collection rate (MCR), and tracheal mucus rheology using anesthetized C57BL\/6 mice. The cystic fibrosis transmembrane conductance regulator (CFTR) blocker 5-nitro-2-(3-phenylpropylamino)benzoate (NPPB) was also used as a pretreatment for MCh. After collecting baseline mucus for 1.5 h, mucus secretion was stimulated by instilling 5 \u03bcl of 10\u22122 M MCh or UTP around the upper trachea. There was a significant increase in PD after MCh or UTP stimulation (\u221221.3 \u00b1 2.0 mV MCh versus \u221214.1 \u00b1 1.6 mV control; \u221225.4 \u00b1 2.5 mV UTP versus \u221219.2 \u00b1 1.9 mV control). When UTP administration was preceded by DIDS, PD shifted from \u221215.2 \u00b1 2.9 to \u221212.0 \u00b1 2.2 mV. When MCh was preceded by DIDS or by NPPB, there was no change in PD. There was a significant decrease in mucus rigidity index, logG*, with MCh (2.54 \u00b1 0.09 versus 2.99 \u00b1 0.14 for control), similar to that previously reported in other species. With UTP, 14 of 16 mice responded in terms of PD becoming more negative, and of these, there was a significant difference in logG* after UTP administration (2.29 \u00b1 0.10 versus 2.57 \u00b1 0.10 for control), whereas there was no change in logG* with DIDS administration before UTP. When DIDS administration preceded MCh, there was a diminished but still significant decrease in logG* from control, whereas there was no change in logG* when NPPB was preadministered. The control mucus collection rate was 0.19 \u00b1 0.09 mg\/h, whereas after MCh stimulation, it increased to 2.83 \u00b1 0.78 mg\/h. No significant difference was measured in the MCR after either UTP or DIDS+UTP stimulation. DIDS+MCh and NPPB+MCh both resulted in significant increases in MCR, but of a much smaller magnitude than that for MCh alone. We conclude that hypersecretion owing to UTP in C57BL\/6 mice is less vigorous than with MCh, reflecting the limited population of Ca2+-dependent Cl\u2212 channels stimulated by UTP P2 receptors. The action of MCh on tracheal mucus secretion in mice appears to involve both CFTR- and non-CFTR-dependent chloride channels.<\/jats:p>","DOI":"10.1165\/ajrcmb.22.3.3610","type":"journal-article","created":{"date-parts":[[2013,4,3]],"date-time":"2013-04-03T21:39:08Z","timestamp":1365025148000},"page":"373-379","source":"Crossref","is-referenced-by-count":4,"title":["Effects of Methacholine and Uridine 5\u2032-Triphosphate on Tracheal Mucus Rheology in Mice"],"prefix":"10.1093","volume":"22","author":[{"given":"Eiichi","family":"Sudo","sequence":"first","affiliation":[{"name":"Pulmonary Research Group, University of Alberta, Edmonton, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Pulmonary Research Group, University of Alberta, Edmonton, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William A.","family":"Boyd","sequence":"additional","affiliation":[{"name":"Pulmonary Research Group, University of Alberta, Edmonton, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malcolm","family":"King","sequence":"additional","affiliation":[{"name":"Pulmonary Research Group, University of Alberta, Edmonton, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2000,3,1]]},"reference":[{"key":"2026030700083783800_B1","first-page":"833","article-title":"Cystic fibrosis (review).","volume":"113","author":"Wood","year":"1976","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026030700083783800_B2","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1126\/science.256.5058.774","article-title":"Cystic fibrosis: molecular biology and therapeutic implications (review).","volume":"256","author":"Collins","year":"1992","journal-title":"Science"},{"key":"2026030700083783800_B3"},{"key":"2026030700083783800_B4","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1056\/NEJM199108223250802","article-title":"Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis.","volume":"325","author":"Knowles","year":"1991","journal-title":"N. Engl. J. Med."},{"key":"2026030700083783800_B5","doi-asserted-by":"crossref","first-page":"C911","DOI":"10.1152\/ajpcell.1997.272.3.C911","article-title":"cGMP stimulates sodium and chloride currents in rat tracheal airway epithelia.","volume":"272","author":"Schwiebert","year":"1997","journal-title":"Am. J. Physiol."},{"key":"2026030700083783800_B6","first-page":"321","article-title":"Interstrain differences in murine submucosal glands.","volume":"14S","author":"Cowley","year":"1997","journal-title":"Pediatr. Pulmonol."},{"key":"2026030700083783800_B7","first-page":"A133","article-title":"Tracheal mucus rheology and response to methacholine in CFTR-knockout mice.","volume":"157","author":"King","year":"1998","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026030700083783800_B8"},{"key":"2026030700083783800_B9","doi-asserted-by":"crossref","first-page":"C348","DOI":"10.1152\/ajpcell.1992.263.2.C348","article-title":"Chloride secretory response to extracellular ATP in human normal and cystic fibrosis nasal epithelia.","volume":"263","author":"Clarke","year":"1992","journal-title":"Am. J. Physiol."},{"key":"2026030700083783800_B10","doi-asserted-by":"crossref","first-page":"C1478","DOI":"10.1152\/ajpcell.1994.266.5.C1478","article-title":"Hyperabsorption of Na+ and raised Ca2+-mediated Cl\u2212 secretion in nasal epithelia of CF mice.","volume":"266","author":"Grubb","year":"1994","journal-title":"Am. J. Physiol."},{"key":"2026030700083783800_B11","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1165\/ajrcmb.10.4.8136152","article-title":"Effect of ATP and UTP on fluid transport by human nasal epithelial cells in culture.","volume":"10","author":"Benali","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2026030700083783800_B12","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1089\/jam.1997.10.25","article-title":"Acute effects of uridine 5\u2032-triphosphate on mucociliary clearance in isolated frog palate.","volume":"10","author":"Festa","year":"1997","journal-title":"J. Aerosol. Med."},{"key":"2026030700083783800_B13","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1073\/pnas.89.5.1621","article-title":"Regulation of Cl\u2212 channels in normal and cystic fibrosis airway epithelial cells by extracellular ATP.","volume":"89","author":"Stutts","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026030700083783800_B14"},{"key":"2026030700083783800_B15","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1183\/09031936.93.06010067","article-title":"Rheology of mucus and epithelial potential difference: small airways vs. trachea.","volume":"6","author":"App","year":"1993","journal-title":"Eur. Respir. J."},{"key":"2026030700083783800_B16","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1152\/jappl.1977.42.6.797","article-title":"Rheological properties of microliter quantities of normal mucus.","volume":"42","author":"King","year":"1977","journal-title":"J. Appl. Physiol."},{"key":"2026030700083783800_B17"},{"key":"2026030700083783800_B18","first-page":"589","article-title":"Role of mucus viscoelasticity in cough clearance.","volume":"24","author":"King","year":"1987","journal-title":"Biorheology"},{"key":"2026030700083783800_B19","first-page":"322","article-title":"Rheology of mouse tracheal mucus.","volume":"14S","author":"King","year":"1997","journal-title":"Pediatr. Pulmonol."},{"key":"2026030700083783800_B20","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1183\/09031936.93.06010076","article-title":"Ferret tracheal mucus rheology, clearability and volume following administration of substance P or methacholine.","volume":"6","author":"De Sanctis","year":"1993","journal-title":"Eur. Respir. J."},{"key":"2026030700083783800_B21","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1164\/ajrccm\/137.3.707","article-title":"Sampling technique and rheology of human bronchial mucus.","volume":"137","author":"Jeanneret-Grosjean","year":"1988","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026030700083783800_B22"},{"key":"2026030700083783800_B23","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1006\/pulp.1995.1035","article-title":"A comparison of a new mucolytic N-acetylcysteine L-lysinate with N-acetylcysteine: airway epithelial function and mucus changes in dog.","volume":"8","author":"Tomkiewicz","year":"1995","journal-title":"Pulmon. Pharmacol."},{"key":"2026030700083783800_B24","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1126\/science.8211164","article-title":"Altered fluid transport across airway epithelium in cystic fibrosis.","volume":"262","author":"Jiang","year":"1993","journal-title":"Science"},{"key":"2026030700083783800_B25","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1089\/jam.1995.8.167","article-title":"Effects of aerosolized amiloride on mucociliary transport velocity and transepithelial potential difference in isolated frog palate.","volume":"8","author":"Festa","year":"1995","journal-title":"J. Aerosol. Med."},{"key":"2026030700083783800_B26"},{"key":"2026030700083783800_B27","doi-asserted-by":"crossref","first-page":"L159","DOI":"10.1152\/ajplung.1994.267.2.L159","article-title":"Extracellular ATP regulation of feline tracheal submucosal gland secretion.","volume":"267","author":"Shimura","year":"1994","journal-title":"Am. J. Physiol. (Lung Cell Mol. Physiol. 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