Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice

AUTOR(ES)

Hedlund, Petter

FONTE

The National Academy of Sciences

RESUMO

The generation of nitric oxide (NO) in penile erectile tissue and the subsequent elevation of cyclic GMP (cGMP) levels are important for normal penile erection. Current treatments of erectile dysfunction elevate either cGMP levels by blocking cGMP degrading phosphodiesterase 5 or cyclic AMP (cAMP) levels by intrapenile injection of prostaglandin E1. The molecular target or targets of cGMP in erectile tissue and the role of cAMP for normal penile erection are not known. Herein, we report that mice lacking cGMP-dependent kinase I (cGKI) have a very low ability to reproduce and that their corpora cavernosa fail to relax on activation of the NO/cGMP signaling cascade. Elevation of cAMP by forskolin, however, induces similar relaxation in normal and cGKI-null corpus cavernosum. In addition, sperm derived from cGKI-null mice is normal, can undergo acrosomal reactions, and can efficiently fertilize eggs. Altogether, these data identify cGKI as the downstream target of cGMP in erectile tissue and provide evidence that cAMP signaling cannot compensate for the absence of the cGMP/cGKI signaling cascade in vivo.

Documentos Relacionados

• Immunohistochemical localization of cyclic GMP-dependent protein kinase in mammalian brain.
• Purification and characterization of 3':5'-cyclic GMP-dependent protein kinase.
• Localization of cyclic GMP-dependent protein kinase and substrate in mammalian cerebellum.
• Toxoplasma gondii Cyclic GMP-Dependent Kinase: Chemotherapeutic Targeting of an Essential Parasite Protein Kinase
• Activation of hormone-sensitive lipase and phosphorylase kinase by purified cyclic GMP-dependent protein kinase