Activation of protein kinase A stimulates the progesterone-induced calcium influx in human sperm exposed to the phosphodiesterase inhibitor papaverine.
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.
Torres-Flores
Víctor
V
Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México. Ciudad Universitaria, Apartado Postal 70-297 México, DF, México.
Hernández-Rueda
Yadira Libertad
YL
Neri-Vidaurri
Paloma del Carmen
Pdel C
Jiménez-Trejo
Francisco
F
Calderón-Salinas
Víctor
V
Molina-Guarneros
Juan A
JA
González-Martínez
Marco T
MT
D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010208:Papaverine / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011374:Progesterone / Q000378:metabolism*; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism
D010726:Phosphodiesterase Inhibitors; D011374:Progesterone; D010208:Papaverine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium