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In vitro and in vivo studies on the importance of the soluble guanylyl cyclase α1 subunit in penile erection

Kelly Decaluwé, Sofie Nimmegeers UGent, Robrecht Thoonen UGent, Emanuel Buys, Peter Brouckaert UGent and Johan Van de Voorde UGent (2010) WORLD JOURNAL OF UROLOGY. 28(5). p.643-650
abstract
Soluble guanylyl cyclase (sGC), which plays a pivotal role in penile erection, is a heterodimer build up by an alpha and a beta subunit. For both subunits two isoforms have been characterized, but only the sGC alpha(1)beta(1) and sGC alpha(2)beta(1) isoforms seem to be functionally active. To elucidate the functional role of the sGC alpha(1)beta(1) heterodimer in the mechanism of erection, experiments were performed in vivo and on isolated corpora cavernosa (CC) using sGC alpha (1) (-/-) mice. For the in vivo study sGC-dependent and -independent vasorelaxing agents were injected intracavernosally in sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice and the rise in intracavernosal pressure was recorded. For the in vitro study, isolated CC tissues from sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice were mounted in organ baths for isometric tension recording and concentration-dependent curves were obtained for sGC-dependent and -independent vasorelaxing agents. These experiments were performed on 2 different mice strains (129SvEvS7 and C57BL6/J) to determine potential strain differences. The responses in sGC alpha (1) (-/-) after administration of the NO-donors, sodium nitroprusside (SNP) and spermine-NO, and to electrical stimulation are significantly reduced although not completely abolished. Responses to sGC-independent vasorelaxing agents are similar in sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice from both strains suggesting that the decreased potential of smooth muscle relaxation is not related to structural changes or changes in the pathway downstream sGC. This study illustrates the strain-independent importance of the sGC alpha(1)beta(1) heterodimer, although remaining vasorelaxing responses in the sGC alpha (1) (-/-) mice suggest a complementary role for the sGC alpha(2)beta(1) isoform or (an) sGC-independent mechanism(s).
Please use this url to cite or link to this publication:
author
organization
alternative title
In vitro and in vivo studies on the importance of the soluble guanylyl cyclase alfa1 subunit in penile erection
year
type
journalArticle (original)
publication status
published
subject
keyword
GMP PATHWAY, DYSFUNCTION, CORPUS CAVERNOSUM, CONTRACTILITY, MICE, ACTIVATORS, NITRIC-OXIDE, penile erection, nitric oxide, soluble guanylyl cyclase, erectile dysfunction
journal title
WORLD JOURNAL OF UROLOGY
World J. Urol.
volume
28
issue
5
pages
643 - 650
Web of Science type
Article
Web of Science id
000282122700017
JCR category
UROLOGY & NEPHROLOGY
JCR impact factor
2.438 (2010)
JCR rank
23/68 (2010)
JCR quartile
2 (2010)
ISSN
0724-4983
DOI
10.1007/s00345-010-0509-7
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1088958
handle
http://hdl.handle.net/1854/LU-1088958
date created
2010-12-17 11:08:14
date last changed
2016-12-19 15:46:18
@article{1088958,
  abstract     = {Soluble guanylyl cyclase (sGC), which plays a pivotal role in penile erection, is a heterodimer build up by an alpha and a beta subunit. For both subunits two isoforms have been characterized, but only the sGC alpha(1)beta(1) and sGC alpha(2)beta(1) isoforms seem to be functionally active. To elucidate the functional role of the sGC alpha(1)beta(1) heterodimer in the mechanism of erection, experiments were performed in vivo and on isolated corpora cavernosa (CC) using sGC alpha (1) (-/-) mice.
For the in vivo study sGC-dependent and -independent vasorelaxing agents were injected intracavernosally in sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice and the rise in intracavernosal pressure was recorded. For the in vitro study, isolated CC tissues from sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice were mounted in organ baths for isometric tension recording and concentration-dependent curves were obtained for sGC-dependent and -independent vasorelaxing agents. These experiments were performed on 2 different mice strains (129SvEvS7 and C57BL6/J) to determine potential strain differences.
The responses in sGC alpha (1) (-/-) after administration of the NO-donors, sodium nitroprusside (SNP) and spermine-NO, and to electrical stimulation are significantly reduced although not completely abolished. Responses to sGC-independent vasorelaxing agents are similar in sGC alpha (1) (-/-) and sGC alpha (1) (+/+) mice from both strains suggesting that the decreased potential of smooth muscle relaxation is not related to structural changes or changes in the pathway downstream sGC.
This study illustrates the strain-independent importance of the sGC alpha(1)beta(1) heterodimer, although remaining vasorelaxing responses in the sGC alpha (1) (-/-) mice suggest a complementary role for the sGC alpha(2)beta(1) isoform or (an) sGC-independent mechanism(s).},
  author       = {Decaluw{\'e}, Kelly and Nimmegeers, Sofie and Thoonen, Robrecht and Buys, Emanuel  and Brouckaert, Peter and Van de Voorde, Johan},
  issn         = {0724-4983},
  journal      = {WORLD JOURNAL OF UROLOGY},
  keyword      = {GMP PATHWAY,DYSFUNCTION,CORPUS CAVERNOSUM,CONTRACTILITY,MICE,ACTIVATORS,NITRIC-OXIDE,penile erection,nitric oxide,soluble guanylyl cyclase,erectile dysfunction},
  language     = {eng},
  number       = {5},
  pages        = {643--650},
  title        = {In vitro and in vivo studies on the importance of the soluble guanylyl cyclase \ensuremath{\alpha}1 subunit in penile erection},
  url          = {http://dx.doi.org/10.1007/s00345-010-0509-7},
  volume       = {28},
  year         = {2010},
}

Chicago
Decaluwé, Kelly, Sofie Nimmegeers, Robrecht Thoonen, Emanuel Buys, Peter Brouckaert, and Johan Van de Voorde. 2010. “In Vitro and in Vivo Studies on the Importance of the Soluble Guanylyl Cyclase Α1 Subunit in Penile Erection.” World Journal of Urology 28 (5): 643–650.
APA
Decaluwé, K., Nimmegeers, S., Thoonen, R., Buys, E., Brouckaert, P., & Van de Voorde, J. (2010). In vitro and in vivo studies on the importance of the soluble guanylyl cyclase α1 subunit in penile erection. WORLD JOURNAL OF UROLOGY, 28(5), 643–650.
Vancouver
1.
Decaluwé K, Nimmegeers S, Thoonen R, Buys E, Brouckaert P, Van de Voorde J. In vitro and in vivo studies on the importance of the soluble guanylyl cyclase α1 subunit in penile erection. WORLD JOURNAL OF UROLOGY. 2010;28(5):643–50.
MLA
Decaluwé, Kelly, Sofie Nimmegeers, Robrecht Thoonen, et al. “In Vitro and in Vivo Studies on the Importance of the Soluble Guanylyl Cyclase Α1 Subunit in Penile Erection.” WORLD JOURNAL OF UROLOGY 28.5 (2010): 643–650. Print.