Download cGMP: Generators, Effectors and Therapeutic Implications by Harald H. H. W. Schmidt, Franz B. Hofmann, Johannes-Peter PDF
By Harald H. H. W. Schmidt, Franz B. Hofmann, Johannes-Peter Stasch
After the invention of endogenous NO formation within the overdue '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 booklet is an enthusiastic occasion of cyclic guanosine monophosphate (cGMP) and amply illustrates the significance of this box of technological know-how to sufferers and how within which the sphere has developed. it really is solely dedicated to this fascinating and critical signaling molecule, addressing all fresh advances in knowing guanylate cyclase legislation, NO/sGC interactions, cGMP effector mechanisms and their pathophysiological and pharmacological implications. specific awareness can also be given to scientific functions of the radical cGMP-elevating medications that are at the horizon, hence spanning the continuum from uncomplicated technology to sanatorium.
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Additional info for cGMP: Generators, Effectors and Therapeutic Implications
Example text
2005; Makino et al. 2003; Martin et al. 2005). These effects are complicated as the small molecules change both the population of 6-coordinate FeII -CO and produce a small population of 5-coordinate FeII -CO. Some investigators have placed significant weight on the formation of a 5-coordinate FeII -CO complex and propose that the species is highly active. However, the FeII -CO complex in the presence of YC-1 and GTP is a mixture of three different species, and there is currently no evidence tying a specific activity with any one of these species.
Biochem J 335(Pt 1):125–130 Russwurm M, Koesling D (2004) NO activation of guanylyl cyclase. EMBO J 23:4443–4450 Sanders KM, Ward SM, Thornbury KD, Dalziel HH, Westfall DP, Carl A (1992) Nitric-oxide as a nonadrenergic, noncholinergic neurotransmitter in the gastrointestinal-tract. Jpn J Pharmacol 58:220–225 Biochemistry of Soluble Guanylate Cyclase 31 Sayed N, Baskaran P, Ma X, van den Akker F, Beuve A (2007) Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation. Proc Natl Acad Sci USA 104:12312–12317 Shiga T, Suzuki N (2005) Amphipathic alpha-helix mediates the heterodimerization of soluble guanylyl cyclase.
Obviously, only a fraction of normal NO-GC content in the vessel wall is sufficient to control blood pressure. For the other NO-GC1 KO strain (Buys et al. 2008), gender-dependent hypertension was reported with higher blood pressure for male than female mice (147 vs. 118 mmHg). Hypertension was age- (after 14 weeks) and testosterone-dependent as prevented by orchidectomy and treatment with an androgen receptor antagonist. The discrepancy in gender-dependent hypertension may very well be related to the genetic background of the animals as the NO-GC1 KOs Genetic Mouse Models of the NO Receptor ‘Soluble’ Guanylyl Cyclases 41 are either on a mixed 129/C57BL6 (Mergia et al.