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Department of Biochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978; and Department of Life Sciences, Bar-Ilan University, Ramat Gan 52900, Israel
Acrosomal exocytosis
in mammalian spermatozoa is a process essential for fertilization. We
report here that atrial natriuretic peptide (ANP) markedly stimulates
acrosomal exocytosis of capacitated human spermatozoa. Typically, ANP
exerts some of its actions via activation of the ANP receptor (ANPR-A),
a particulate guanylyl cyclase-linked receptor, and subsequent
formation of guanosine 3',5'-cyclic monophosphate (cGMP).
We found that ANP-stimulated acrosome reaction was inhibited by the
competitive ANPR-A antagonist anantin, indicating a receptor-mediated
process. A linear fragment of ANP, ANP-(13
28), and another ANP-like
compound, brain natriuretic peptide, were inactive. The stimulatory
effect of ANP on acrosome reaction was mimicked by the permeable cGMP
analog, 8-bromo-cGMP (8-BrcGMP). Addition of the protein kinase C (PKC)
inhibitors, staurosporine and GF-109203X, resulted in a dose-related
inhibition of ANP-induced acrosome reaction. Also, downregulation of
endogeneous PKC activity resulted in inhibition of ANP- but not
8-BrcGMP-induced acrosome reaction. Removal of extracellular
Ca2+ abolished ANP-induced
acrosome reaction. Thus ANP via
Ca2+ influx, PKC activation, and
stimulation of particulate guanylyl cyclase may play a role in the
induction of acrosome reaction of human spermatozoa.
acrosome reaction; guanosine 3',5'-cyclic monophosphate; calcium; protein kinase C
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