Brouckaert, Peter

Buys, Emmanuel

Decaluwé, Kelly

Nimmegeers, Sofie

Sips, Patrick

Van de Voorde, Johan

English

Ghent University Academic Bibliography

ROLE OF THE SOLUBLE GUANYLYL CYCLASE 1 SUBUNIT IN MICE CORPUS CAVERNOSUM SMOOTH MUSCLE RELAXATION Nimmegeers1 S., Sips2 P., Buys2 E., Decaluwe1 K., Brouckaert2 P., Van de Voorde1 J. 1Department of Physiology and Physiopathology 2Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology, Ghent University, Ghent, 9000, Belgium As the major effector molecule for NO, soluble guanylyl cyclase (sGC) plays a key role within the NO/cGMP signalling cascade which participates in penile erection. sGC exists as an -heterodimer, but only two isoforms have been reported to be active (sGC 1 1 and sGC 2 1). The 1 1 isoform is predominantly present in penile tissue. The functional importance of the 1-subunit in corpus cavernosum (CC) smooth muscle relaxation was assessed by mounting isolated CC from sGC 1-/- mice and wild type littermates in organ baths for isometric tension recording. The endothelium-dependent relaxation to acetylcholine (ACh) and the neurogenic response to electrical field stimulation (EFS) were nearly abolished in the sGC 1-/- CC. The relaxing influence of exogenous NO (from sodium nitroprusside (SNP) and NO-gas), was significantly decreased in the sGC 1-/- mice. The remaining relaxation induced by exogenous NO in the sGC 1-/- mice was strongly but not completely inhibited by the sGC-inhibitor ODQ. In the preparations of the sGC 1-/- mice, the response to BAY 41-2272 (NO-independent sGC-activator) was also significantly reduced. The specificity of the impairment of the sGC-related responses was demonstrated by the unaffected response to forskolin (adenylyl cyclase activator) and 8-pCPT-cGMP (cGMP-analogue). In conclusion, our findings indicate the involvement of the predominant isoform sGC 1 1 in NO-induced CC smooth muscle relaxation. However, the remaining relaxing influence of exogenous NO in the sGC 1-/- mice suggests that also the less abundantly expressed isoform sGC 2 1 and/or(an) sGC-independent mechanism(s) has a substantial role in NO-related corporal smooth muscle relaxation.  

Role of the soluble guanylyl cyclase 1 subunit in mice corpus cavernosum smooth muscle relaxation

https://biblio.ugent.be/publication/1149969/file/1179127

Role of the soluble guanylyl cyclase 1 subunit in mice corpus cavernosum smooth muscle relaxation

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Ghent University Academic Bibliography