Brouckaert, Peter

Buys, Emmanuel

Nimmegeers, Sofie

Sips, Patrick

Van de Voorde, Johan

English

Ghent University Academic Bibliography

ROLE OF THE SOLUBLE GUANYLYL CYCLASE α1 β1 (sGCα1β1) ISOFORM IN MICE CORPUS CAVERNOSUM SMOOTH MUSCLE RELAXATION Nimmegeers S1, Sips P2, Buys E2, Brouckaert P2, Van de Voorde J1 1Department of Physiology and Physiopathology, Ghent University, Ghent, Belgium, 2Department of Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology and Ghent University, Ghent, 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. The enzyme exist as an αβ-heterodimer, but only two isoforms have been reported to be active (sGCα1β1 and sGCα2β1). The functional importance of the α1-subunit in corpus cavernosum (CC) smooth muscle relaxation was assessed by mounting CC from male sGCα1-/- mice and wild type littermates in organ baths for isometric tension recording. The endothelium-dependent relaxation to acetylcholine (ACh) or bradykinin (BK) and the neurogenic response to electrical field stimulation (EFS) were nearly abolished in the sGCα1-/- CC. The relaxing influence of exogenous NO (from sodium nitroprusside (SNP) and NO-gas) was also significantly decreased in the sGCα1-/- mice. The remaining relaxation seen in the sGCα1-/- mice with exogenous NO, was strongly but not completely inhibited by the sGC-inhibitor ODQ. In the preparations of the sGCα1-/- mice, the response to BAY 41–2272 (NO-independent sGC-stimulator) and to T-1032 (phosphodiesterase type 5 inhibitor) were also significantly reduced. The specificity of the impairment of the sGC-related responses was demonstrated by the similar forskolin (adenylyl cyclase activator) and 8 pCPT-cGMP (cGMP-analogue)-induced responses. In conclusion, our findings indicate the involvement of an sGC isoform with the α1-subunit in NO-induced CC smooth muscle relaxation. However, the remaining relaxing influence of exogenous NO in the sGCα1-/- mice, suggests the contribution of (an) additional pathway(s). 

Role of the soluble guanylyl cyclase α1 β1 (sGCα1β1) isoform in mice corpus cavernosum smooth muscle relaxation

https://biblio.ugent.be/publication/1151921/file/1179091

Role of the soluble guanylyl cyclase α1 β1 (sGCα1β1) isoform in mice corpus cavernosum smooth muscle relaxation

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Ghent University Academic Bibliography