{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T02:15:32Z","timestamp":1785204932917,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,2,4]],"date-time":"2005-02-04T00:00:00Z","timestamp":1107475200000},"content-version":"vor","delay-in-days":6854,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[1986,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The relative toxicity of numerous cardiotonic steroids (viz. ouabain, digitoxin, digoxin, convallatoxin, SC4453, bufalin, gitaloxin, digoxigenin, actodigin, oleandrin, digitoxigenin, gitoxin, strophanthidin, gitoxigenin, lanatosides A, B and C, \u03b1\u2010 and \u03b2\u2010acetyl digoxin, \u03b1\u2010 and \u03b2\u2010methyl digoxin) and related compounds towards a number of independent cell lines established from human, monkey, mouse, Syrian hamster, and Chinese hamster have been determined. All cardiac glycosides and their genins, as well as the cardiotonic alkaloid cassaine, exhibited &gt; 100\u2010fold higher toxicity towards cultured human and monkey cells in comparison to the cell lines of mouse, Syrian hamster, and Chinese hamster origins. These differences are species\u2010related as all cell lines (both normal as well as transformed) from any one species, as well as cells from the closely related species (e.g., man and monkey or mouse, Chinese hamster, and Syrian hamster), showed similar sensitivity towards these drugs. The failure to see any significant differences in cellular toxicity for a larger number of other compounds which either bear limited structural resemblance to cardiac glycosides (viz. estradiol 17\u2010\u03b2\u2010acetate, testosterone propionate, 21\u2010acetoxy pregnenolone, \u03b2\u2010estradiol, digitonin, tigogenin, and tomatine) or interact with the Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup> ATPase in a different manner (viz. veratridine, sanguinarine nitrate, penicillic acid, vanadium pentoxide, harmaline\u2010HCI, 5,5\u2032\u2010diphenyl hydantoin, quindonium bromide, and methyl quinolizinum bromide) provides strong evidence that the observed species\u2010related differences are highly specific for cardiotonic steroids. Studies on the binding of [<jats:sup>3<\/jats:sup>H]ouabain show that, in comparison to human and monkey cell lines, no significant binding of the drug is observed in cells derived from the resistant species (i.e., mouse and Chinese hamster). The Na<jats:sup>+<\/jats:sup>\/K<jats:sup>+<\/jats:sup> ATPase from cells of the resistant species is inhibited at much higher concentrations of ouabain and digitoxin in comparison to the enzyme from human cells, and a good correlation is observed between these concentrations and those reported for inhibition of the enzyme from isolated heart muscles of the same species. These results provide strong evidence that the species\u2010related differences in sensitivity to digitalis have a cellular basis and that the cultured cells from various mammalian species provide a useful model system for investigating the mechanism of action of cardiac glycosides.<\/jats:p>","DOI":"10.1002\/jcp.1041270202","type":"journal-article","created":{"date-parts":[[2005,2,26]],"date-time":"2005-02-26T13:30:02Z","timestamp":1109424602000},"page":"197-206","source":"Crossref","is-referenced-by-count":98,"title":["Cellular basis for the species differences in sensitivity to cardiac glycosides (digitalis)"],"prefix":"10.1002","volume":"127","author":[{"given":"Radhey S.","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Chopra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn K.","family":"Stetsko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,2,4]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"187","article-title":"The role of Na+, K+\u2010ATPase in the inotropic action of digitalis","volume":"29","author":"Akera T.","year":"1978","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_1_3_1","first-page":"17","article-title":"The effect of ouabain on sodium\u2010potassium activated adenosinetriphosphatase from the hearts of several mammalian species","volume":"170","author":"Akera T.","year":"1969","journal-title":"J. Pharmacol. Exp. Therap."},{"key":"e_1_2_1_4_1","first-page":"42","article-title":"Possible explanation for the insensitivity of the rat to cardiac glycosides","volume":"168","author":"Allen J. C.","year":"1969","journal-title":"J. Pharmacol. Exp. Therap."},{"key":"e_1_2_1_5_1","first-page":"(93)","volume-title":"Biogenesis and Turnover of Membrane Macromolecules","author":"Baker R. M.","year":"1976"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(74)90149-4"},{"key":"e_1_2_1_7_1","first-page":"229","article-title":"Binding of digitalis derivatives to beef, cat and human cardiac (Na+ + K+) ATPase: Affinity and kinetic constants","volume":"271","author":"Brown L.","year":"1984","journal-title":"Arch. Internat. Pharmacodyn. et de Therapie"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(77)90098-7"},{"key":"e_1_2_1_9_1","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1073\/pnas.77.2.1101","article-title":"Isolation of diploid human lymphoblast mutants presumably homozygous for ouabain resistance","volume":"77","author":"Choy W. N.","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01542924"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.43.070174.001551"},{"key":"e_1_2_1_12_1","first-page":"1119","article-title":"Comparative pharmacology of cardiac glycosides","volume":"26","author":"Detweiler D. K.","year":"1967","journal-title":"Fed. Proc."},{"key":"e_1_2_1_13_1","first-page":"393","article-title":"Observations on the chromosomes of Chinese hamster cells in tissue culture","volume":"21","author":"Ford D. K.","year":"1958","journal-title":"J. Nat. Cancer Inst."},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041030206"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(81)90490-1"},{"key":"e_1_2_1_16_1","doi-asserted-by":"crossref","first-page":"(6843)","DOI":"10.1016\/S0021-9258(18)88857-3","article-title":"Cross\u2010resistance and biochemical studies with two classes of HeLa cell mutants resistant to cardiac glycosides. The Unusual behavior of cardenolide SC4453","volume":"260","author":"Gupta R. S.","year":"1985","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_17_1","first-page":"143","article-title":"Interaction of cardiac glycosides with (Na+ + K +) activated ATPase A biochemical link to digitalis induced inotropy","volume":"36","author":"Hansen O.","year":"1984","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_1_18_1","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1093\/genetics\/55.3.513","article-title":"Genetics of somatic mammalian cells. IV. Properties of Chinese hamster cell mutant with respect to requirement for proline","volume":"55","author":"Kao F. T.","year":"1967","journal-title":"Genetics"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(63)90007-7"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(85)90792-0"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1040790314"},{"key":"e_1_2_1_22_1","first-page":"653","volume-title":"The Pharmacological Basis of Therapeutics","author":"Moe G. K.","year":"1975"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/14.9.495"},{"key":"e_1_2_1_24_1","first-page":"1125","article-title":"Species differences in duration of action of cardiac glycosides","volume":"26","author":"Okita G. T.","year":"1967","journal-title":"Fed. Proc."},{"key":"e_1_2_1_25_1","first-page":"449","article-title":"Origins of the different sensitivities of (Na+ + K+)\u2010dependent adenosine\u2010triphosphatase preparations to ouabain","volume":"76","author":"Periyasamy S.","year":"1983","journal-title":"Comp. Biochem. Physiol."},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(79)90612-9"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.103.2.273"},{"key":"e_1_2_1_28_1","first-page":"47","volume-title":"New Aspects of Cardiac Glycosides","author":"Repke K.","year":"1963"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(65)90269-8"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00642a600"},{"key":"e_1_2_1_31_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/jcp.1040850114","article-title":"Variant HeLa cells selected for their resistance to ouabain J","volume":"85","author":"Rosenberg H. M.","year":"1975","journal-title":"Cell. Physiol."},{"key":"e_1_2_1_32_1","first-page":"3","article-title":"The sodiumpotassium adenosine triphosphatase: pharmacological, physiological and biochemical aspects","volume":"27","author":"Schwartz A.","year":"1975","journal-title":"Pharmacol. Rev."},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1965.45.3.596"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0033-0620(84)90012-4"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/2031355a0"},{"key":"e_1_2_1_36_1","first-page":"209","volume-title":"Methods in Cell Biology","author":"Thompson L. H.","year":"1973"},{"key":"e_1_2_1_37_1","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/0006-2952(72)90305-X","article-title":"Rates of dissociation of enzymeouabain complexes and K0.5 values in (Na+ + K+) adenosine triphosphatase from different species","volume":"21","author":"Tobim T.","year":"1972","journal-title":"Biochem. Pharmacol."},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(76)90300-9"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(72)90201-5"},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.17.2.299"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.1041270202","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.1041270202","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,21]],"date-time":"2023-10-21T10:21:16Z","timestamp":1697883676000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.1041270202"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1986,5]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1986,5]]}},"alternative-id":["10.1002\/jcp.1041270202"],"URL":"https:\/\/doi.org\/10.1002\/jcp.1041270202","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[1986,5]]}}}