Source:http://linkedlifedata.com/resource/pubmed/id/15333581
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2004-8-30
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| pubmed:abstractText |
Female sexual function is under-studied, and mechanisms of clitoral engorgement-relaxation are incompletely understood. Penile erection results from nitric oxide (NO) -induced cyclic guanosine monophosphate (cGMP) accumulation. cGMP-dependent protein kinase (PKG) activates large-conductance, calcium-activated potassium channels (BK(Ca)), thereby hyperpolarizing and relaxing vascular and trabecular smooth muscle cells, allowing engorgement. We hypothesize rat clitorises relax by a similar mechanism. Rat clitorises express components of the proposed pathway: neuronal and endothelial NO synthases, soluble guanylyl cyclase (sGC), type 5 phosphodiesterase (PDE-5), and BK(Ca) channels. The NO donor diethylamine NONOate (DEANO), the PKG activator 8-pCPT-cGMP, and the PDE-5 inhibitor sildenafil, cause dose-dependent clitoral relaxation that is inhibited by antagonists of PKG (Rp-8-Br-cGMPS) or BK(Ca) channels (iberiotoxin). Electrical field stimulation induces tetrodotoxin-sensitive NO release and relaxation that is inhibited by the Na+ channel blocker tetrodotoxin or sGC inhibitor 1H-(1,2,4)oxadiozolo(4,3-a)quinoxalin-1-one. Human BK(Ca) channels, transferred to Chinese hamster ovary cells via an adenoviral vector, and endogenous rat clitoral smooth muscle K+ current are activated by this PKG-dependent mechanism. Laser confocal microscopy reveals protein expression of BK(Ca) channels on clitoral smooth muscle cells; these cells exhibit BK(Ca) channel activity that is activated by both DEANO and sildenafil. We conclude that neurovascular derived NO causes clitoral relaxation via a PKG-dependent activation of BK(Ca) channels. The BK(Ca) channel is an appealing target for drug therapy of female erectile dysfunction.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic GMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Large-Conductance...,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide,
http://linkedlifedata.com/resource/pubmed/chemical/Piperazines,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels...,
http://linkedlifedata.com/resource/pubmed/chemical/Purines,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfones,
http://linkedlifedata.com/resource/pubmed/chemical/sildenafil
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1530-6860
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
18
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1382-91
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:15333581-Animals,
pubmed-meshheading:15333581-CHO Cells,
pubmed-meshheading:15333581-Calcium,
pubmed-meshheading:15333581-Clitoris,
pubmed-meshheading:15333581-Cricetinae,
pubmed-meshheading:15333581-Cyclic GMP,
pubmed-meshheading:15333581-Cyclic GMP-Dependent Protein Kinases,
pubmed-meshheading:15333581-Electric Stimulation,
pubmed-meshheading:15333581-Electrophysiology,
pubmed-meshheading:15333581-Female,
pubmed-meshheading:15333581-Humans,
pubmed-meshheading:15333581-Immunohistochemistry,
pubmed-meshheading:15333581-Large-Conductance Calcium-Activated Potassium Channels,
pubmed-meshheading:15333581-Lasers,
pubmed-meshheading:15333581-Microdissection,
pubmed-meshheading:15333581-Muscle, Smooth,
pubmed-meshheading:15333581-Muscle Relaxation,
pubmed-meshheading:15333581-Nitric Oxide,
pubmed-meshheading:15333581-Piperazines,
pubmed-meshheading:15333581-Potassium Channels, Calcium-Activated,
pubmed-meshheading:15333581-Purines,
pubmed-meshheading:15333581-Rats,
pubmed-meshheading:15333581-Rats, Sprague-Dawley,
pubmed-meshheading:15333581-Signal Transduction,
pubmed-meshheading:15333581-Sulfones
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| pubmed:year |
2004
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| pubmed:articleTitle |
The neurovascular mechanism of clitoral erection: nitric oxide and cGMP-stimulated activation of BKCa channels.
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| pubmed:affiliation |
Department of Medicine (Cardiology) and the Vascular Biology Group, University of Alberta, Edmonton, Canada.
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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