By Harald H. H. W. Schmidt, Franz B. Hofmann, Johannes-Peter Stasch
After the invention of endogenous NO formation within the past due '80s and the 1998 Nobel Prize in body structure or medication, many researchers and physicians back took an interest within the NO/sGC interplay and cGMP-dependent signaling. This ebook is an enthusiastic get together of cyclic guanosine monophosphate (cGMP) and amply illustrates the significance of this box of technology to sufferers and how during which the sector has developed. it's solely dedicated to this fascinating and demanding signaling molecule, addressing all fresh advances in figuring out guanylate cyclase rules, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. specific realization may also be given to medical functions of the radical cGMP-elevating medicines that are at the horizon, hence spanning the continuum from easy technological know-how to health center.
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Extra resources for cGMP: Generators, Effectors and Therapeutic Implications
1 Schematic illustration of the NO receptor GCs and the respective KOs. Shown is the subunit composition of the NO receptor GC isoforms (α1 β1 , α2 β1 ) and the consequences following subunit deletion in the respective KO mice. For further explanation see text. GC, guanylyl cyclase; KO, knock out; cyc, cyclase catalytic domain 36 E. Mergia et al. biochemical and kinetic analysis of both NO-GC1 and NO-GC2 did not reveal any significant differences especially regarding NO sensitivity, thus, the enzymatic regulation of the isoforms appears to be similar.
1 Isoforms of the NO Receptor Guanylyl Cyclase . . . . . . . . . . . . . . . 2 Genetic Mouse Models . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 34 36 44 Abstract The NO/cGMP signalling cascade has an important role in smooth muscle relaxation, inhibition of platelet aggregation and neuronal transmission. Although the function of the main NO receptor GC (NO-GC) is well established, the particular tasks of the NO receptor isoforms (NO-GC1 and NO-GC2) are unclear and NO targets other than NO-GC have been postulated.
The results are in good agreement with the abrogated endothelium-induced relaxation in the cGKI (Pfeifer et al. 1998) and eNOS KO mice (Huang et al. 1995; Chataigneau et al. 1999). Smooth Muscle Relaxation in Corpus Cavernosum of NO-GC1 KO Mice Smooth muscle relaxation is the key event in blood filling of the corporal tissue and restriction of venous outflow being required for penile erection (Andersson and Wagner 1995). The important role of NO/cGMP is underlined by the efficiency of the phosphodiesterase 5 inhibitor Sildenafil as today’s most successful therapy for the treatment of erectile dysfunction.