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In vitro and in vivo studies on the importance of the soluble gyanylyl cyclase alpha 1 subunit in penile erection

Background

Penile erection is a highly regulated physiologic event in which the NO-cGMP pathway plays a pivotal role. NO derived from both non-cholinergic non-adrenergic nerves and endothelial cells diffuses to the arterial and corporal smooth muscle cells to bind and activate its target soluble guanylyl cyclase (sGC). The following increase in cGMP induces a cascade of events eventually leading to smooth muscle relaxation and penile erection. Because of its central role sGC seems to be an attractive and promising new target for the treatment of erectile dysfunction. Structurally, sGC is a heterodimer consisting of an α and a β subunit. Of both subunits, two isoforms have been characterised, however only the sGCα1β1 and sGCα2β1 heterodimers are functionally active.

Materials and methods

In order to elucidate the functional role of the sGCα1β1 heterodimer in the mechanism of erection, experiments were performed in vivo and on isolated corpora cavernosa (CC) using sGCα1-/- mice. For the in vivo study the responses to electrical stimulation of the nervus cavernosus and intracavernosal injection of different sGC-dependent and -independent vasodilatory agents were investigated. For the in vitro study isolated CC tissues from sGCα1-/- and sGCα1+/+ mice were mounted in organ baths for isometric tension recording and the responses to different sGC-dependent and -independent vasorelaxing agents were examined.

Results

The responses in sGCα1-/- to administration of sodium nitroprusside (1 – 4 μg/kg or 10-9 – 10-5 mol) and spermine/NO (10 – 20 μg/kg or 10-9 – 10-5 mol) and to electrical stimulation (5 – 15 Hz, 8 V, 60 s or 1 – 8 Hz, 80 V, 20 s) are significantly reduced although not completely abolished. Responses to sGC-independent vasorelaxing agents are similar between sGCα1-/- and sGCα1+/+ mice suggesting that the decreased potential of smooth muscle relaxation is not related to structural changes or changes in the pathway downstream sGC.

Conclusion

This study clearly illustrates the importance of the sGCα1β1 heterodimer, however the results also provide evidence that besides activation of sGCα1β1 also other mechanisms are involved in penile erection such as sGCα2β1 and/or sGC-independent mechanisms.

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Correspondence to Kelly Decaluwé.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Decaluwé, K., Nimmegeers, S., Thoonen, R. et al. In vitro and in vivo studies on the importance of the soluble gyanylyl cyclase alpha 1 subunit in penile erection. BMC Pharmacol 9, P10 (2009). https://doi.org/10.1186/1471-2210-9-S1-P10

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Keywords

  • Erectile Dysfunction
  • Nitroprusside
  • Guanylyl Cyclase
  • Corpus Cavernosa
  • Smooth Muscle Relaxation