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A new prostaglandin E receptor mediates calcium influx and acrosome reaction in human spermatozoa

1998; National Academy of Sciences; Volume: 95; Issue: 6 Linguagem: Inglês

10.1073/pnas.95.6.3008

1091-6490

Michael Schaefer, Thomas Hofmann, Günter Schultz, Thomas Gudermann,

Reproductive Physiology in Livestock

Zona pellucida protein 3, a protein of the egg’s extracellular matrix, and progesterone secreted by granulosa cells surrounding the oocyte are regarded as physiological stimuli of sperm acrosome reaction. Signal transduction steps initiated by both stimuli result in influx of Ca 2+ from the extracellular space. Herein, we propose a role for prostaglandin (PG) E as a physiological inducer of Ca 2+ influx and acrosome reaction in human spermatozoa. PGE 1 specifically binds to human sperm membranes ( K d = 20.4 nM; B max = 88 fmol/mg protein) and induces a pertussis toxin-insensitive, transient increase in intracellular Ca 2+ concentrations, which can be blocked by μM concentrations of La 3+ , Gd 3+ , and Zn 2+ . The kinetic profile was similar to that observed after progesterone challenge. Sequential application of both agonists did not lead to cross-desensitization. E prostaglandins were found to be the only prostanoids with agonistic properties (EC 50 values for PGE 1 and PGE 2 : <10 nM and 300 nM, respectively). Pharmacological characteristics were not compatible with those of cloned prostanoid receptors indicating the expression of a distinct membrane receptor. Activation of the sperm E prostanoid receptor stimulates incorporation of [α- 32 P]GTP azidoanilide into immunoprecipitated Gα q/11 subunits. Thus, in human sperm, PG induces Ca 2+ influx and acrosome reaction via a G q/11 -coupled E prostanoid receptor. The block of PGE 1 -induced Ca 2+ transients and acrosome reaction by physiological Zn 2+ concentrations highlights a role of Zn 2+ as an endogenous Ca 2+ channel blocker present in seminal plasma protecting sperm from premature PGE 1 -evoked increases in intracellular Ca 2+ concentrations.