Guanylate cyclase activator

A guanylate cyclase activator (or "GUCA") is a member of a group of proteins that upregulate guanylate cyclase. GUCA is also known as guanylate cyclase-activating protein (or "GCAP"). Its mutations can be associated with vision defects.^[1]

There are five genes involved:

GUCA1A, GUCA1B, GUCA1C
GUCA2A, GUCA2B

There are several therapeutic drugs that act as GUCAs, including linaclotide and plecanatide, which are guanylate cyclase-C receptor agonists. These drugs increase the secretion of bicarbonate and chloride in the colon and potentially relieve visceral hypersensitivity in IBS-C patients.^[2]

Guanyl cyclase targeting drug, Cinaciguat has emerged in recent years has one of the first in the class of soluble guanyl cyclase inhibitor. Soluble guanyl class is a version of guanyl cyclase that has a primary preference for nitric oxide(NO) sensitivity, with some variants beings more insensitive to NO than others but still remaining soluble within the cell cytosol^[3]. Cinaciguat targets the specifically the soluble form of guanyl cyclase. This guanyl that triggers reduced blood flow through GTP to cGMP conversion. The cGMP acts as a secondary messenger to target reduced blood flow pathways. This pathway has been linked to several cardiovascular diseases, such as ADHF(acute decompensated heart failure) which Cinaciguat has been developed to target^[4].

References

^ Payne AM, Downes SM, Bessant DA, et al. (1998). "A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1". Hum. Mol. Genet. 7 (2): 273–7. doi:10.1093/hmg/7.2.273. PMID 9425234.
^ Saps, Miguel; Miranda, Adrian (2017), Greenwood-Van Meerveld, Beverley (ed.), "Gastrointestinal Pharmacology", Handbook of Experimental Pharmacology, 239, Cham: Springer International Publishing: 147–176, doi:10.1007/164_2016_119, ISBN 978-3-319-56359-6, PMID 28236087, retrieved 2024-04-27
^ Estancial, Camila S.; Rodrigues, Renata L.; De Nucci, Gilberto; Antunes, Edson; Mónica, Fabiola Z. (2015). "Pharmacological characterisation of the relaxation induced by the soluble guanylate cyclase activator, BAY 60-2770 in rabbit corpus cavernosum". BJU International. 116 (4): 657–664. doi:10.1111/bju.13105. ISSN 1464-410X. PMID 25715977.
^ Sawabe, Toshihiro; Chiba, Toshiki; Kobayashi, Akihiro; Nagasaka, Kosuke; Aihara, Kazuyuki; Takaya, Akiyuki (2019). "A novel soluble guanylate cyclase activator with reduced risk of hypotension by short-acting vasodilation". Pharmacology Research & Perspectives. 7 (2): e00463. doi:10.1002/prp2.463. ISSN 2052-1707. PMC 6399102. PMID 30873284.

External links

Guanylate+Cyclase-Activating+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

[pmid94252343-1] Payne AM, Downes SM, Bessant DA, et al. (1998). "A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1". Hum. Mol. Genet. 7 (2): 273–7. doi:10.1093/hmg/7.2.273. PMID 9425234.

[2] Saps, Miguel; Miranda, Adrian (2017), Greenwood-Van Meerveld, Beverley (ed.), "Gastrointestinal Pharmacology", Handbook of Experimental Pharmacology, 239, Cham: Springer International Publishing: 147–176, doi:10.1007/164_2016_119, ISBN 978-3-319-56359-6, PMID 28236087, retrieved 2024-04-27

[3] Estancial, Camila S.; Rodrigues, Renata L.; De Nucci, Gilberto; Antunes, Edson; Mónica, Fabiola Z. (2015). "Pharmacological characterisation of the relaxation induced by the soluble guanylate cyclase activator, BAY 60-2770 in rabbit corpus cavernosum". BJU International. 116 (4): 657–664. doi:10.1111/bju.13105. ISSN 1464-410X. PMID 25715977.

[4] Sawabe, Toshihiro; Chiba, Toshiki; Kobayashi, Akihiro; Nagasaka, Kosuke; Aihara, Kazuyuki; Takaya, Akiyuki (2019). "A novel soluble guanylate cyclase activator with reduced risk of hypotension by short-acting vasodilation". Pharmacology Research & Perspectives. 7 (2): e00463. doi:10.1002/prp2.463. ISSN 2052-1707. PMC 6399102. PMID 30873284.

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