Journal of Andrology Testis Workshop 2009
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published-Ahead-of-Print April 1, 2006, DOI:10.2164/jandrol.05152

This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
27/4/568    most recent
Author Manuscript (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Anderson, R. A.
Right arrow Articles by Zaneveld, L. J.D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Anderson, R. A.
Right arrow Articles by Zaneveld, L. J.D.

SAMMA induces premature human acrosomal loss by Ca2+ signaling dysregulation

Robert A. Anderson , Kenneth A. Feathergill , Donald P. Waller , and Lourens J.D. Zaneveld

SAMMA is licensed for development as a contraceptive microbicide. Understanding mechanisms of its biological activity is prerequisite to designing more active second generation products. This study examined Ca2+ involvement in SAMMA-induced premature acrosomal loss (SAL) in noncapacitated human spermatozoa. SAMMA causes acrosomal loss (AL) in a dose-dependent manner (ED50 = 0.25 g/mL). SAL requires extracellular Ca2+ (ED50 = 85 M). SAL is inhibited by verapamil (non-specific voltage-dependent Ca2+ channel blocker; IC50 = 0.4 M), diphenylhydantoin and NiCl2 (T-type (Cav3.x) channel blockers; IC50 210 M and 75 M, respectively). Verapamil blockade of L-type (Cav1.x)channels is use-dependent; activated channels are more sensitive to inhibition. However, verapamil inhibition of SAL does not increase after repeated SAMMA stimulation. SAL is unaffected by 10 M nifedipine (selective L-type channel blocker). This contrasts to 40% inhibition (p < 0.001) of AL induced by 1 M thapsigargin (Ca2+-ATPase inhibitor; releases intracellular Ca2+ stores, promotes capacitative Ca2+ entry). SAL is unaffected by 1 M BAPTA-AM (intracellular Ca2+ chelator), and 50 M 2-APB (blocks InsP3 receptors and store-operated channels). This contrasts with thapsigargin-induced AL, inhibited nearly 65% by BAPTA-AM (p < 0.005) and 91% by 2-APB (p < 0.001). The results suggest that SAL is mediated by Ca2+ entry through channels pharmacologically similar to the T-type (Cav3.2) class. This process appears distinct from that due to physiological stimuli such as progesterone or zona pellucida-derived proteins. SAMMA's contraceptive activity may be due to induction of premature AL through dysregulation of Ca2+ signaling.




This article has been cited by other articles:


Home page
 J AndrolHome page
R. A. Anderson, K. A. Feathergill, C. J. Chany II, S. Jain, and A. Krunic
Nitric Oxide-Dependent Human Acrosomal Loss Induced by PPCM (SAMMA) and by Nitric Oxide Donors Occurs by Independent Pathways: Basis for Synthesis of an Improved Contraceptive Microbicide
J Androl, March 1, 2009; 30(2): 168 - 182.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2006 by The American Society of Andrology.