{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:21:12Z","timestamp":1773422472858,"version":"3.50.1"},"reference-count":33,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[1999,6,1]],"date-time":"1999-06-01T00:00:00Z","timestamp":928195200000},"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":[[1999,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Mechanisms of Na+ and K+ transport across the basolateral membrane of isolated Malpighian tubules of Drosophila melanogaster were studied by examining the effects of ion substitution and putative inhibitors of specific ion transporters on fluid secretion rates, basolateral membrane potential and secreted fluid cation composition. Inhibition of fluid secretion by [(dihydroindenyl) oxy]alkanoic acid (DIOA) and bumetanide (10\u22124 mol l\u22121) suggested that a K+:Cl\u2212 cotransporter is the main route for K+ entry into the principal cells of the tubules. Differences in the effects of bumetanide on fluxes of K+ and Na+ are inconsistent with effects upon a basolateral Na+:K+:2Cl\u2212 cotransporter. Large differences in electrical potential across apical (&amp;gt;100 mV, lumen positive) and basolateral (&amp;lt;60 mV, cell negative) cell membranes suggest that a favourable electrochemical gradient for Cl\u2212 entry into the cell may be used to drive K+ into the cell against its electrochemical gradient, via a DIOA-sensitive K+:Cl\u2212 cotransporter. A Na+\/K+-ATPase was also present in the basolateral membrane of the Malpighian tubules. Addition of 10\u22125 to 10\u22123 mol l\u22121 ouabain to unstimulated tubules depolarized the basolateral potential, increased the Na+ concentration of the secreted fluid by 50\u201373 % and increased the fluid secretion rate by 10\u201319 %, consistent with an increased availability of intracellular Na+. We suggest that an apical vacuolar-type H+-ATPase and a basolateral Na+\/K+-ATPase are both stimulated by cyclic AMP. In cyclic-AMP-stimulated tubules, K+ entry is stimulated by the increase in the apical membrane potential, which drives K+:Cl\u2212 cotransport at a faster rate, and by the stimulation of the Na+\/K+-ATPase. Fluid secretion by cyclic-AMP-stimulated tubules was reduced by 26 % in the presence of ouabain, suggesting that the Na+\/K+-ATPase plays a minor role in K+ entry into the tubule cells. Malpighian tubules secreted a Na+-rich (150 mmol l\u22121) fluid at high rates when bathed in K+-free amino-acid-replete saline (AARS). Secretion in K+-free AARS was inhibited by amiloride and bafilomycin A1, but not by bumetanide or hydrochlorothiazide, which inhibit Na+:Cl\u2212 cotransport. There was no evidence for a Na+ conductance in the basolateral membrane of unstimulated or cyclic-AMP-stimulated tubules. Possible mechanisms of Na+ entry into the tubule cells include cotransport with organic solutes such as amino acids and glucose.<\/jats:p>","DOI":"10.1242\/jeb.202.11.1561","type":"journal-article","created":{"date-parts":[[2021,4,25]],"date-time":"2021-04-25T05:21:37Z","timestamp":1619328097000},"page":"1561-1570","source":"Crossref","is-referenced-by-count":86,"title":["Contributions of K+:Cl\u2212 cotransport and Na+\/K+-ATPase to basolateral ion transport in malpighian tubules of <i>Drosophila melanogaster<\/i>"],"prefix":"10.1242","volume":"202","author":[{"given":"Stuart M.","family":"Linton","sequence":"first","affiliation":[{"name":"McMaster University Department of Biology , , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. J.","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"McMaster University Department of Biology , , 1280 Main Street West, Hamilton, Ontario, Canada L8S 4K1"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1999,6,1]]},"reference":[{"key":"2024121801263324600_JEXBIO_202_11_1561C1","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1016\/0022-1910(75)90240-1","article-title":"Relationship of Na+\u2013K+-activated ATPase to fluid production by Malpighian tubules of Locusta migratoria","volume":"21","author":"Anstee","year":"1975","journal-title":"J. Insect Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C2","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/0022-1910(79)90002-7","article-title":"Fluid and cation secretion by the Malpighian tubules of Locusta","volume":"25","author":"Anstee","year":"1979","journal-title":"J. Insect Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C3","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/0005-2736(68)90145-4","article-title":"Studies on (Na+\u2013K+)-activated ATPase. XX. Properties of (Na+\u2013K+)-activated ATPase in rat liver","volume":"150","author":"Bakkeren","year":"1968","journal-title":"Biochim. Biophys. Acta"},{"key":"2024121801263324600_JEXBIO_202_11_1561C4","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/0022-1910(88)90133-3","article-title":"Microelectrode studies on Malpighian tubule cells of Locusta migratoria: Effects of external ions and inhibitors","volume":"34","author":"Baldrick","year":"1988","journal-title":"J. Insect Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C5","doi-asserted-by":"publisher","first-page":"3385","DOI":"10.1242\/jeb.201.24.3385","article-title":"Epithelial glucose transport by lobster antennal gland","volume":"201","author":"Behnke","year":"1998","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C6","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/0010-406X(66)90134-4","article-title":"Studies on sodium\u2013potassium-activated adenosinetriphosphatase. XV. The rectal gland of elasmobranchs","volume":"17","author":"Bonting","year":"1966","journal-title":"Comp. Biochem. Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C7","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1111\/j.1469-7793.1998.235bi.x","article-title":"Protein kinase A induces recruitment of active Na+,K+-ATPase units to the plasma membrane of rat proximal convoluted tubule cells","volume":"511","author":"Carranza","year":"1998","journal-title":"J. Physiol., Lond"},{"key":"2024121801263324600_JEXBIO_202_11_1561C8","first-page":"R1321","article-title":"CAP2b, a cardioacceleratory peptide, is present in Drosophila and stimulates fluid secretion by Malpighian tubules via cyclic GMP","volume":"269","author":"Davies","year":"1995","journal-title":"Am. J. Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C9","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/0022-1910(95)00018-P","article-title":"A cellular pathway for Cl\u2212 during fluid secretion in ant Malpighian tubules: evidence from ion-sensitive microelectrode studies?","volume":"41","author":"Dijkstra","year":"1995","journal-title":"J. Insect Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C10","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1242\/jeb.197.1.421","article-title":"The Malpighian tubules of Drosophila melanogaster: a novel phenotype for studies of fluid secretion and its control","volume":"197","author":"Dow","year":"1994","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C11","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/0300-9629(88)90663-9","article-title":"Human red cell volume regulation in hypotonic media","volume":"90A","author":"Ellory","year":"1988","journal-title":"Comp. Biochem. Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C12","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1242\/jeb.106.1.25","article-title":"Mechanism and control of hyperosmotic NaCl-rich secretion by the rectal gland of Squalus acanthias","volume":"106","author":"Epstein","year":"1983","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C13","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1007\/BF01923405","article-title":"Effects of corpora cardiaca extract, furosemide and ion substitution on sodium and chloride flux in perfused Malpighian tubules of Locusta","volume":"49","author":"Fogg","year":"1993","journal-title":"Experientia"},{"key":"2024121801263324600_JEXBIO_202_11_1561C14","first-page":"696","article-title":"Demonstration of a [K+,Cl\u2212]-cotransport system in human red cells by its sensitivity to [(dihydroindenyl)oxy]alkanoic acids: regulation of cell swelling and distinction from the bumetanide sensitive [Na+,K+,Cl\u2212]-cotransport system","volume":"33","author":"Garay","year":"1988","journal-title":"Molec. Pharmac"},{"key":"2024121801263324600_JEXBIO_202_11_1561C15","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1111\/j.1469-7793.1998.225bi.x","article-title":"Differential oxygen sensitivity of the K+\u2013Cl\u2212 cotransporter in normal and sickle human red blood cells","volume":"11","author":"Gibson","year":"1998","journal-title":"J. Physiol., Lond"},{"key":"2024121801263324600_JEXBIO_202_11_1561C16","doi-asserted-by":"publisher","first-page":"C521","DOI":"10.1152\/ajpcell.1991.261.3.C521","article-title":"Dibutyryl cyclic AMP activates bumetanide-sensitive electrolyte transport in Malpighian tubules","volume":"261","author":"Hegarty","year":"1991","journal-title":"Am. J. Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C17","first-page":"F550","article-title":"Cloning, characterization and gene organization of K\u2013Cl cotransporter from pig and human kidney and C. elegans","volume":"275","author":"Holtzman","year":"1998","journal-title":"Am. J. Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C18","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1085\/jgp.97.4.799","article-title":"Okadaic acid inhibition of KCl cotransport. Evidence that protein phosphorylation is necessary for activation of transport by either cell swelling or N-ethylmaleimide","volume":"97","author":"Jennings","year":"1991","journal-title":"J. Gen. Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C19","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1146\/annurev.ph.58.030196.003245","article-title":"Molecular mechanisms of NaCl cotransport","volume":"58","author":"Kaplan","year":"1996","journal-title":"Annu. Rev. Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C20","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1002\/j.1460-2075.1989.tb03364.x","article-title":"Molecular characterization and expression of the (Na++K+)-ATPase \u03b1-subunit in Drosophila melanogaster","volume":"8","author":"Lebovitz","year":"1989","journal-title":"EMBO J"},{"key":"2024121801263324600_JEXBIO_202_11_1561C21","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1242\/jeb.195.1.123","article-title":"Mechanisms of K+ uptake across the basal membrane of Malpighian tubules of Formica polyctena: The effects of ions and inhibitors","volume":"195","author":"Leyssens","year":"1994","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C22","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1242\/jeb.172.1.417","article-title":"Insect Malpighian tubules: V-ATPase action in ion and fluid transport","volume":"172","author":"Maddrell","year":"1992","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C23","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1242\/jeb.177.1.287","article-title":"Gramicidin switches transport in insect epithelia from potassium to sodium","volume":"177","author":"Maddrell","year":"1993","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C24","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1242\/jeb.177.1.273","article-title":"The regulation of haemolymph potassium activity during initiation and maintenance of diuresis in fed Rhodnius prolixus","volume":"177","author":"Maddrell","year":"1993","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C25","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1242\/jeb.137.1.265","article-title":"Stimulation of sodium transport and fluid secretion by ouabain in an insect Malpighian tubule","volume":"137","author":"Maddrell","year":"1988","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C26","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1242\/jeb.201.14.2091","article-title":"The electroneutral cation\u2013chloride transporters","volume":"201","author":"Mount","year":"1998","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C27","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1242\/jeb.199.5.1163","article-title":"Separate control of anion and cation transport in Malpighian tubules of Drosophila melanogaster","volume":"199","author":"O\u2019Donnell","year":"1996","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C28","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1242\/jeb.110.1.275","article-title":"Secretion by the Malpighian tubules of Rhodnius prolixus St\u00e5l: electrical events","volume":"110","author":"O\u2019Donnell","year":"1984","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C29","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1242\/jeb.198.8.1647","article-title":"Fluid reabsorption and ion transport by the lower Malpighian tubules of adult female Drosophila","volume":"198","author":"O\u2019Donnell","year":"1995","journal-title":"J. Exp. Biol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C30","first-page":"R1039","article-title":"Hormonally-controlled chloride movement across Drosophila tubules is via ion channels in stellate cells","volume":"43","author":"O\u2019Donnell","year":"1998","journal-title":"Am. J. Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C31","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1161\/01.HYP.18.3.316","article-title":"Effects of three sodium\u2013potassium adenosine triphosphatase inhibitors","volume":"18","author":"Pamnani","year":"1991","journal-title":"Hypertension"},{"key":"2024121801263324600_JEXBIO_202_11_1561C32","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1152\/ajplegacy.1969.216.3.547","article-title":"Na\u2013K-activated adenosine triphosphatase and pancreatic secretion in the dog","volume":"216","author":"Riddlestap","year":"1969","journal-title":"Am. J. Physiol"},{"key":"2024121801263324600_JEXBIO_202_11_1561C33","first-page":"R339","article-title":"Dibutyryl-cyclic AMP increases basolateral sodium conductance of mosquito Malpighian tubules","volume":"248","author":"Sawyer","year":"1985","journal-title":"Am. J. Physiol"}],"container-title":["Journal of Experimental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.biologists.com\/jeb\/article-pdf\/202\/11\/1561\/3595208\/jexbio_202_11_1561.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/jeb\/article-pdf\/202\/11\/1561\/3595208\/jexbio_202_11_1561.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T01:26:47Z","timestamp":1734485207000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/jeb\/article\/202\/11\/1561\/7941\/Contributions-of-K-Cl-cotransport-and-Na-K-ATPase"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,6,1]]},"references-count":33,"journal-issue":{"issue":"11","published-print":{"date-parts":[[1999,6,1]]}},"URL":"https:\/\/doi.org\/10.1242\/jeb.202.11.1561","relation":{},"ISSN":["0022-0949","1477-9145"],"issn-type":[{"value":"0022-0949","type":"print"},{"value":"1477-9145","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,6,1]]}}}