liu.seSök publikationer i DiVA
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Erectile dysfunction in cyclic CMP-dependent kinase I-deficient mice
Lund University Hospital.
University of Lund.
The Salk Institute.
Technische Universität, München.
Visa övriga samt affilieringar
2000 (Engelska)Ingår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 97, nr 5, s. 2349-2354Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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.

Penile erection is produced by an increased blood flow to the corpus cavernosum (CC), made possible by opening of penile resistance vessels (helicine arteries), relaxation of the CC cells, and occlusion of the venous outflow (1). The erectile response in several animal models depends on nitric oxide (NO), produced by nerves as well as vascular endothelium (1, 2–4). NO activates soluble guanylate cyclase, which leads to the production of cyclic GMP (cGMP). cGMP signals via three different receptors in eukaryotic cells, including ion channels, phosphodiesterases, and protein kinases (5). At present, however, the molecular targets that are activated by cGMP and finally execute the relaxation of penile smooth muscle are not known. In addition, two different cGMP-dependent protein kinases (cGKI and cGKII) have been identified in mammals (6, 7). cGKII is expressed in the small intestine, brain, and cartilage (8–10), whereas high levels of cGKI are found in vascular and intestinal smooth muscle, platelets, Purkinje cells of the cerebellum, and CC cells (11, 12). Inactivation of cGKI in mice abolished both NO/cGMP-dependent relaxation of vascular and intestinal smooth muscle and inhibition of platelet aggregation, causing hypertension, intestinal dysmotility, and abnormal hemostasis (13). In the present study, we investigated the function of cGKI in erectile tissue and the capability of cGKI-deficient mice to reproduce. Furthermore, we analyzed whether a cross-talk exists between the cGMP and cyclic AMP (cAMP) signaling cascades in smooth muscle (5, 14), i.e., whether cAMP can cause relaxation via cGKI.

Ort, förlag, år, upplaga, sidor
National Academy of Sciences; 1999 , 2000. Vol. 97, nr 5, s. 2349-2354
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:liu:diva-59772ISI: 85633200071OAI: oai:DiVA.org:liu-59772DiVA, id: diva2:353379
Tillgänglig från: 2010-09-26 Skapad: 2010-09-24 Senast uppdaterad: 2017-12-12

Open Access i DiVA

Fulltext saknas i DiVA

Övriga länkar

Link to article

Personposter BETA

Hedlund, Petter

Sök vidare i DiVA

Av författaren/redaktören
Hedlund, Petter
I samma tidskrift
Proceedings of the National Academy of Sciences of the United States of America
Medicin och hälsovetenskap

Sök vidare utanför DiVA

GoogleGoogle Scholar

urn-nbn

Altmetricpoäng

urn-nbn
Totalt: 62 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf