{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,30]],"date-time":"2023-09-30T09:41:01Z","timestamp":1696066861306},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2006,7,11]],"date-time":"2006-07-11T00:00:00Z","timestamp":1152576000000},"content-version":"vor","delay-in-days":4362,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[1994,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The calcium channel antagonist, bepridil, \u03b2\u2010(2\u2010methylpropoxy)methyl\u2010N\u2010phenyl\u2010N\u2010(phenylemethyl)\u20101\u2010pyrrolidineethanamine monocholoride monohydrate, inhibits the sickling of deoxygenated sickle (SS) erythrocytes, as determined by light microscopy. The antisickling effect was seen only in dilute suspensions of red cells. In concentrated erythrocyte suspensions, sickling was not inhibited and measurements of hematocrit and cell density were unchanged by bepridil. The determination of cell volume in dilute suspensions was complicated by bepridil's tendency to aggregate, but rapid measurements by electronic sizing also indicated no increase in cell volume, up to a bepridil concentration of 200 \u03bcM. Ektacytometry of dilute sickle cell suspensions suggested an explanation for the anti\u2010sickling action of bepridil. Osmotic scan ektacytometry disclosed that bepridil initially increased the surface area of the red cell, as shown by a shift in the low osmolality minimum. This change was complete in 10 sec, the shortest time that could be measured. Subsequently, at concentrations that were observed to inhibit the sickling of deoxygenated sickle cells (100 \u03bcM or greater), red cells underwent a loss in surface area that was complete in 1 min. There was a concomitant loss of cell deformability. Light and scanning electron microscopy has previously shown that bepridil is a stomatocytic agent. Using transmission electron microscopy, we verified that the loss of surface area was a consequence of endocytosis, presumably as the end stage of the stomatocytic transformation induced by bepridil. Bepridil did not inhibit intracellular hemoglobin S polymerization even at 200 \u03bcM, as shown by oxygen scan ektacytometry. Bepridil thus appears to inhibit the sickling of deoxygenated SS cells by inducing endocytosis and lowering cell deformability. This mechanism may explain the anti\u2010sickling effect of other basic amphiphiles, such as chlorpromazine. \u00a9 1994 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajh.2830460410","type":"journal-article","created":{"date-parts":[[2007,2,21]],"date-time":"2007-02-21T13:42:43Z","timestamp":1172065363000},"page":"310-318","source":"Crossref","is-referenced-by-count":1,"title":["Bepridil as an antisickling agent: Membrane internalization and cell rigidity"],"prefix":"10.1002","volume":"46","author":[{"given":"Robert M.","family":"Johnson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clemenceau","family":"Acquaye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claude","family":"F\u00e9o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharada","family":"Sarnaik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,11]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)90951-7"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V70.5.1245.1245"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V61.5.899.899"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/26.10.1435"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109888"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.990030412"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(89)73004-4"},{"key":"e_1_2_1_9_2","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1182\/blood.V66.2.432.432","article-title":"Evaluation of covalent antisickling compounds by PO2 scan ektacytometry","volume":"66","author":"Johnson RM","year":"1985","journal-title":"Blood"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(85)90799-4"},{"key":"e_1_2_1_11_2","first-page":"247","article-title":"Rheological action of bepridil on normal and sickle erythrocytes","volume":"9","author":"Stuart J","year":"1989","journal-title":"Clin Hemorheol"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(69)86461-1"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(69)86462-3"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.3109\/00365518109097426"},{"key":"e_1_2_1_15_2","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1182\/blood.V67.4.1110.1110","article-title":"Red cell rheology in stomatocyte\u2010echinocyte transformation: Roles of cell geometry and cell shape","volume":"67","author":"Reinhart W","year":"1986","journal-title":"Blood"},{"key":"e_1_2_1_16_2","first-page":"668","article-title":"Determination of density distribution of red cell population","volume":"64","author":"Danon D","year":"1964","journal-title":"J Lab Clin Med"},{"key":"e_1_2_1_17_2","first-page":"1","article-title":"The contribution of normal and pathologic erythrocytes to blood rheology","volume":"7","author":"LaCelle P","year":"1971","journal-title":"Prog Hematol"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(68)90078-3"},{"key":"e_1_2_1_19_2","first-page":"71","article-title":"Former echinocytaires et stomatocytaires du globule rouge. 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