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NO/cGMP signalling
BMC Pharmacology volume 5, Article number: S10 (2005)
Most of the effects of the signalling molecule nitric oxide (NO) are mediated by the stimulation of the NO-sensitive guanylyl cyclase (GC) and the subsequent increase in cGMP formation. The enzyme contains a prosthetic heme group which mediates NO stimulation. In addition to the physiological activator NO, NO-sensitisers like the substance YC-1 sensitise the enzyme towards NO and may therefore have important pharmacological implications. Two isoforms of NO-sensitive GC have been identified to date that share regulatory properties but differ in the subcellular localization; the more ubiquitously expressed α1β1 heterodimer and the α2β1 isoform mainly expressed in brain. Knock-out mice in which either one the GC subunits is deleted will provide information about the functional roles of GC and the isoforms.
In intact cells, NO-induced cGMP signalling not only depends on cGMP formation but is also critically determined by the activity of the enzyme responsible for cGMP degradation i.e. phosphodiesterase 5 (PDE5). Recently, direct activation of PDE5 by cGMP was demonstrated which is limiting the cGMP increase and therefore is functioning as a negative feedback. As the cGMP-induced PDE5 activation turned out to be sustained, in the range of hours, it is probably responsible for the NO-induced desensitisation observed within NO/cGMP signalling.
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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 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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Koesling, D., Mergia, E., Russwurm, M. et al. NO/cGMP signalling. BMC Pharmacol 5 (Suppl 1), S10 (2005). https://doi.org/10.1186/1471-2210-5-S1-S10
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DOI: https://doi.org/10.1186/1471-2210-5-S1-S10