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SAMMA causes acrosomal loss (AL) in a dose\u2010dependent manner (ED<jats:sub>50<\/jats:sub>= 0.25 \u03bcg\/mL). SAL requires extracellular Ca<jats:sup>2+<\/jats:sup>(ED<jats:sub>50<\/jats:sub>= 85 \u03bcM). SAL is inhibited by verapamil (nonspecific voltage\u2010dependent Ca<jats:sup>2+<\/jats:sup>channel blocker; IC<jats:sub>50<\/jats:sub>= 0.4 \u03bcM), diphenylhydantoin and NiCl<jats:sub>2<\/jats:sub>(T\u2010type [Ca<jats:sub>v<\/jats:sub>3.x] channel blockers; IC<jats:sub>50<\/jats:sub>210 \u03bcM and 75 \u03bcM, respectively). Verapamil blockade of L\u2010type (Ca<jats:sub>v<\/jats:sub>1.x) channels is use\u2010dependent; activated channels are more sensitive to inhibition. However, verapamil inhibition of SAL does not increase after repeated SAMMA stimulation. SAL is unaffected by 10 \u03bcM nifedipine (selective L\u2010type channel blocker). This contrasts to 40% inhibition (<jats:italic>P<\/jats:italic>&lt; .001) of AL induced by 1 \u03bcM thapsigargin (Ca<jats:sup>2+<\/jats:sup>\u2010ATPase inhibitor; releases intracellular Ca<jats:sup>2+<\/jats:sup>stores, promotes capacitative Ca<jats:sup>2+<\/jats:sup>entry). SAL is unaffected by 1 \u03bcM BAPTA\u2010AM (intracellular Ca<jats:sup>2+<\/jats:sup>chelator), and 50 \u03bcM 2\u2010APB (blocks InsP3 receptors and store\u2010operated channels). This contrasts with thapsigargin\u2010induced AL, inhibited nearly 65% by BAPTA\u2010AM (<jats:italic>P<\/jats:italic>&lt; .005) and 91% by 2\u2010APB (P, .001). The results suggest that SAL is mediated by Ca<jats:sup>2+<\/jats:sup>entry through channels pharmacologically similar to the T\u2010type (Ca<jats:sub>v<\/jats:sub>3.2) class. This process appears distinct from that caused by physiological stimuli such as progesterone or zona pellucida\u2010derived proteins. SAMMA's contraceptive activity may be caused by induction of premature AL through dysregulation of Ca<jats:sup>2+<\/jats:sup>signaling.<\/jats:p>","DOI":"10.2164\/jandrol.05152","type":"journal-article","created":{"date-parts":[[2006,7,18]],"date-time":"2006-07-18T20:21:09Z","timestamp":1153254069000},"page":"568-577","source":"Crossref","is-referenced-by-count":11,"title":["SAMMA Induces Premature Human Acrosomal Loss by Ca<sup>2+<\/sup>Signaling Dysregulation"],"prefix":"10.1002","volume":"27","author":[{"given":"Robert A.","family":"Anderson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth A.","family":"Feathergill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald P.","family":"Waller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourens J. 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