The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice
Open accessAbstract
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 .
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Citations
Cites
Oral Sildenafil in the Treatment of Erectile Dysfunction
Goldstein, I., Lue, T. F., Padma-Nathan, H., Rosen, R. C., Steers, W. D., & Wicker, P. A. (1998) · New England Journal of Medicine · doi:10.1056/nejm199805143382001 · Cited by 2,120
Cited by
(2005) · doi:10.1016/j.ucl.2005.08.007 · Cited by 759
PDE5 inhibitors – pharmacology and clinical applications 20 years after sildenafil discovery
Andersson, K. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14205 · Cited by 445
Self-citationPhysiological Substrates of cAMP-Dependent Protein Kinase
Shabb, J. B. (2001) · Chemical Reviews · doi:10.1021/cr000236l · Cited by 373
Münzel, T., Feil, R., Mülsch, A., Lohmann, S. M., Hofmann, F., & Walter, U. (2003) · Circulation · doi:10.1161/01.cir.0000094403.78467.c3 · Cited by 316
Self-citationBivalacqua, T. J., Usta, M. F., Champion, H. C., Kadowitz, P. J., & Hellstrom, W. J. G. (2003) · Journal of Andrology · doi:10.1002/j.1939-4640.2003.tb02743.x · Cited by 268
Metadata
- Authors
- Hedlund, P., Aszódi, A., Pfeifer, A., Alm, P., Hofmann, F., Ahmad, M., Fässler, R., & Andersson, K.-E.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2000-02-25
- Volume
- 97
- Issue
- 5
- Pages
- 2349-2354
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2152187474
- Cited by
- 198
- References
- 1
- FWCI
- 11.81
- Type
- journal article
- Language
- en
- Open access
- green
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- Hedlund, P., Aszódi, A., Pfeifer, A., Alm, P., Hofmann, F., Ahmad, M., Fässler, R., & Andersson, K.-E. (2000). Erectile dysfunction in cyclic GMP-dependent kinase I-deficient mice. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.030419997
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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