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Published-Ahead-of-Print May 22, 2008, DOI:10.2164/jandrol.107.004614

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Activation of Protein Kinase A Stimulates the Progesterone-Induced Calcium Influx in Human Sperm Exposed to the Phosphodiesterase Inhibitor Papaverine

Victor Torres-Flores , Yadira Libertad Hernández-Rueda , Paloma del Carmen Neri-Vidaurri , Francisco Jiménez-Trejo , Víctor Calderón-Salinas , Juan A. Molina-Guarneros , and Marco T. González-Martínez *

* To whom correspondence should be addressed. E-mail: tuliog{at}servidor.unam.mx.

Progesterone induces a fast transient calcium influx in human sperm though the activation of non genomic receptors. During sperm capacitation, a complex process required for sperm to be able to fertilize the egg, the calcium influx induced by progesterone is enhanced. Sperm capacitation is mediated by an increase in cAMP content and subsequent PKA activation. In this work we examined the effect of increasing intracellular cAMP on the calcium influx induced by progesterone in non capacitated human sperm. To do this, sperm was exposed to the phosphodiesterase inhibitor papaverine for 5 minutes, a treatment that increased both the cAMP content and the PKA activity several-fold. The calcium influx induced by progesterone was increased by papaverine to levels close to those found in capacitated sperm. This effect was partially inhibited by H89 (48 %) and by genistein (41 %) and the sum of both inhibitors reduced the stimulating effect of papaverine by 89 %. The inhibitory effect of gensitein on the progesterone-induced calcium influx could be related to its capability to inhibit the papaverine-stimulated increase in cAMP content and PKA activity. The results presented here suggest that the calcium influx induced by progesterone is up regulated by the PKA activity.



Key words: Sperm • PDE inhibitor • cAMP/PKA • papaverine • pentoxifylline • progesterone







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