{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T21:08:51Z","timestamp":1778274531151,"version":"3.51.4"},"reference-count":0,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1992,11,1]]},"abstract":"<jats:p>We have developed a new test to differentiate between ping-pong and simultaneous mechanisms for tightly coupled anion exchange. This test requires the use of a dead-end reversible noncompetitive inhibitor. As an example, we have applied the test to the anion exchanger of the HL60 cell using the salicylic acid derivative 3,5-diiodosalicylic acid (DIS), which reversibly inhibits HL60 cell Cl\/Cl exchange. The concentration of DIS that causes 50% inhibition (ID50) increased only slightly as either intra- or extracellular chloride was increased, indicating that DIS inhibits HL60 anion exchange in a noncompetitive manner. In agreement with this observation, plots of the slope of the Dixon plot as a function of 1\/[Clo] or 1\/[Cli] were fit with straight lines with nonzero intercepts, indicating that DIS does not compete with either of the substrates ([Clo] and [Cli]). The secondary Dixon slope test is based on the fact that, for a dead-end inhibitor such as DIS, the slope of the Dixon plot slope vs. 1\/[Cli] (secondary Dixon slope or SDS) is independent of extracellular Cl when the exchange mechanism follows ping-pong kinetics. Similarly, the SDS calculated from a plot as a function of 1\/[Clo] is also independent of intracellular Cl for a ping-pong exchanger. In contrast to this prediction, we found that for DIS inhibition of Cl\/Cl exchange in HL60 cells the slope of the Dixon plot slope vs. 1\/[Cli] decreased by a factor of 2.5-fold when [Clo] was increased from 1 to 11 mM (P &amp;lt; 0.0001). This change in the SDS rules out ping-pong kinetics, but is consistent with a simultaneous model of Cl\/Cl exchange in which there are extra- and intracellular anion binding sites, both of which must be occupied by suitable anions in order to allow simultaneous exchange of the ions.<\/jats:p>","DOI":"10.1085\/jgp.100.5.825","type":"journal-article","created":{"date-parts":[[2004,5,13]],"date-time":"2004-05-13T23:48:59Z","timestamp":1084492139000},"page":"825-846","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["A novel method to differentiate between ping-pong and simultaneous exchange kinetics and its application to the anion exchanger of the HL60 cell."],"prefix":"10.1085","volume":"100","author":[{"given":"D","family":"Restrepo","sequence":"first","affiliation":[{"name":"Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B L","family":"Cronise","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R B","family":"Snyder","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P A","family":"Knauf","sequence":"additional","affiliation":[{"name":"Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[1992,11,1]]},"container-title":["The Journal of general physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/100\/5\/825\/1456578\/825.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/100\/5\/825\/1456578\/825.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,21]],"date-time":"2023-07-21T22:28:39Z","timestamp":1689978519000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/100\/5\/825\/26241\/A-novel-method-to-differentiate-between-ping-pong"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,11,1]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1992,11,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.100.5.825","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[1992,11,1]]}}}