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NO/cGMP: The Past, the Present, and the Future

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Guanylate Cyclase and Cyclic GMP

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1020))

Abstract

The NO/cGMP signalling cascade participates in the regulation of physiological parameters such as smooth muscle relaxation, inhibition of platelet aggregation, and neuronal transmission. cGMP is formed in response to nitric oxide (NO) by NO-sensitive guanylyl cyclases that exist in two isoforms (NO-GC1 and NO-GC2). Much has been learned about the regulation of NO-GC; however the precise role of cGMP in complex physiological and especially in pathophysiological settings and its alteration by biological factors needs to be established. Despite reports on a variety of cGMP-independent NO effects, KO mice with a complete lack of NO-GC provide evidence that the vasorelaxing and platelet-inhibiting effects of NO are solely mediated by NO-GC. Isoform-specific KOs demonstrate that low cGMP increases are sufficient to induce smooth muscle relaxation and that either NO-GC isoform is sufficient in most instances outside the central nervous system. In the neuronal system, however, the NO-GC isoforms obviously serve distinct functions as both isoforms are required for long-term potentiation and NO-GC1 was shown to enhance glutamate release in excitatory neurons in the hippocampal CA1 region by gating HCN channels. Future studies have to clarify the role of NO-GC2, to show whether HCN channels are general targets of cGMP in the nervous system and whether the NO/cGMP signalling cascade participates in synaptic transmission in other brain regions.

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Authors and Affiliations

  1. Pharmakologie und Toxikologie Medizinische, Fakultät, Ruhr-Universität Bochum, Bochum, Germany

    Michael Russwurm, Corina Russwurm, Doris Koesling & Evanthia Mergia

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  1. Michael Russwurm
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  2. Corina Russwurm
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  3. Doris Koesling
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  4. Evanthia Mergia
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  1. Addenbrooke’s Hospital, Department of Medicine, University of Cambridge, Hills Road, Cambridge, CB2 2QQ, United Kingdom

    Thomas Krieg

  2. Toxicology and Clinical Pharmacy, Department of Pharmacology, Universität Tübingen, Auf der Morgenstelle 8, Tübingen, 72076, Germany

    Robert Lukowski

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Russwurm, M., Russwurm, C., Koesling, D., Mergia, E. (2013). NO/cGMP: The Past, the Present, and the Future. In: Krieg, T., Lukowski, R. (eds) Guanylate Cyclase and Cyclic GMP. Methods in Molecular Biology, vol 1020. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-459-3_1

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