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Published-Ahead-of-Print May 22, 2008, DOI:10.2164/jandrol.107.004614
Journal of Andrology, Vol. 29, No. 5, September/October 2008
Copyright © American Society of Andrology
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

VÍCTOR TORRES-FLORES*, YADIRA LIBERTAD HERNÁNDEZ-RUEDA*, PALOMA DEL CARMEN NERI-VIDAURRI*, FRANCISCO JIMÉNEZ-TREJO*, VÍCTOR CALDERÓN-SALINAS{dagger}, JUAN A. MOLINA-GUARNEROS* AND MARCO T. GONZÁLEZ-MARTÍNEZ*

From the * Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico; and the {dagger} Departamento de Bioquímica, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Naciona, Mexico.

Correspondence to: Dr Marco T. González-Martínez, Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México. Ciudad Universitaria, CP 04510. Apartado Postal 70-297 México, D.F., México (e-mail: tuliog{at}servidor.unam.mx).


Progesterone induces a fast transient calcium influx in human sperm though the activation of nongenomic 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 protein kinase A (PKA) activation. In this work, we examined the effect of increasing intracellular cAMP on the calcium influx induced by progesterone in noncapacitated human sperm. To do this, sperm were 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 genistein 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: cAMP, intracellular calcium, progesterone







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