Cyclic nucleotide turnover/signalling | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY

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Cyclic nucleotide turnover/signalling

Cyclic nucleotide turnover/signalling C

Contents

Overview
Subfamilies
Further reading
How to cite this family page

Overview

Cyclic nucleotides are second messengers generated by cyclase enzymes from precursor triphosphates and hydrolysed by phosphodiesterases. The cellular actions of these cyclic nucleotides are mediated through activation of protein kinases (cAMP- and cGMP-dependent protein kinases), ion channels (cyclic nucleotide-gated, CNG, and hyperpolarization and cyclic nucleotide-gated, HCN) and guanine nucleotide exchange factors (GEFs, Epac).

Subfamilies

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Adenylyl cyclases (ACs) C
Exchange protein activated by cyclic AMP (EPACs) C
Guanylyl cyclases (GCs) C
- Nitric oxide (NO)-sensitive (soluble) guanylyl cyclase C
- Receptor Guanylyl Cyclase (RGC) family C
Phosphodiesterases, 3',5'-cyclic nucleotide (PDEs) C

Further reading

* Key recommended reading is highlighted with an asterisk

Antoni FA. (2012) New paradigms in cAMP signalling. Mol. Cell. Endocrinol., 353 (1-2): 3-9. [PMID:22085559]

Armani A, Marzolla V, Rosano GM, Fabbri A, Caprio M. (2011) Phosphodiesterase type 5 (PDE5) in the adipocyte: a novel player in fat metabolism?. Trends Endocrinol. Metab., 22 (10): 404-11. [PMID:21741267]

Billington CK, Hall IP. (2012) Novel cAMP signalling paradigms: therapeutic implications for airway disease. Br. J. Pharmacol., 166 (2): 401-10. [PMID:22013890]

Cheepala S, Hulot JS, Morgan JA, Sassi Y, Zhang W, Naren AP, Schuetz JD. (2013) Cyclic nucleotide compartmentalization: contributions of phosphodiesterases and ATP-binding cassette transporters. Annu. Rev. Pharmacol. Toxicol., 53: 231-53. [PMID:23072381]

Chen J, Levin LR, Buck J. (2012) Role of soluble adenylyl cyclase in the heart. Am. J. Physiol. Heart Circ. Physiol., 302 (3): H538-43. [PMID:22058150]

* Cooper DM, Tabbasum VG. (2014) Adenylate cyclase-centred microdomains. Biochem. J., 462 (2): 199-213. [PMID:25102028]

Dekkers BG, Racké K, Schmidt M. (2013) Distinct PKA and Epac compartmentalization in airway function and plasticity. Pharmacol. Ther., 137 (2): 248-65. [PMID:23089371]

* Derbyshire ER, Marletta MA. (2012) Structure and regulation of soluble guanylate cyclase. Annu. Rev. Biochem., 81: 533-59. [PMID:22404633]

Efendiev R, Dessauer CW. (2011) A kinase-anchoring proteins and adenylyl cyclase in cardiovascular physiology and pathology. J. Cardiovasc. Pharmacol., 58 (4): 339-44. [PMID:21978991]

* Francis SH, Blount MA, Corbin JD. (2011) Mammalian cyclic nucleotide phosphodiesterases: molecular mechanisms and physiological functions. Physiol. Rev., 91 (2): 651-90. [PMID:21527734]

García-Osta A, Cuadrado-Tejedor M, García-Barroso C, Oyarzábal J, Franco R. (2012) Phosphodiesterases as therapeutic targets for Alzheimer's disease. ACS Chem Neurosci, 3 (11): 832-44. [PMID:23173065]

Guellich A, Mehel H, Fischmeister R. (2014) Cyclic AMP synthesis and hydrolysis in the normal and failing heart. Pflugers Arch., 466 (6): 1163-75. [PMID:24756197]

Insel PA, Murray F, Yokoyama U, Romano S, Yun H, Brown L, Snead A, Lu D, Aroonsakool N. (2012) cAMP and Epac in the regulation of tissue fibrosis. Br. J. Pharmacol., 166 (2): 447-56. [PMID:22233238]

Keravis T, Lugnier C. (2012) Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments. Br. J. Pharmacol., 165 (5): 1288-305. [PMID:22014080]

* Nicol X, Gaspar P. (2014) Routes to cAMP: shaping neuronal connectivity with distinct adenylate cyclases. Eur. J. Neurosci., 39 (11): 1742-51. [PMID:24628976]

Potter LR. (2011) Guanylyl cyclase structure, function and regulation. Cell. Signal., 23 (12): 1921-6. [PMID:21914472]

Rieg T, Kohan DE. (2014) Regulation of nephron water and electrolyte transport by adenylyl cyclases. Am. J. Physiol. Renal Physiol., 306 (7): F701-9. [PMID:24477683]

Sabbatini ME, Gorelick F, Glaser S. (2014) Adenylyl cyclases in the digestive system. Cell. Signal., 26 (6): 1173-81. [PMID:24521753]

Sanderson TM, Sher E. (2013) The role of phosphodiesterases in hippocampal synaptic plasticity. Neuropharmacology, 74: 86-95. [PMID:23357335]

* Schmidt M, Dekker FJ, Maarsingh H. (2013) Exchange protein directly activated by cAMP (epac): a multidomain cAMP mediator in the regulation of diverse biological functions. Pharmacol. Rev., 65 (2): 670-709. [PMID:23447132]

Seifert R, Lushington GH, Mou TC, Gille A, Sprang SR. (2012) Inhibitors of membranous adenylyl cyclases. Trends Pharmacol. Sci., 33 (2): 64-78. [PMID:22100304]

Sharma S, Kumar K, Deshmukh R, Sharma PL. (2013) Phosphodiesterases: Regulators of cyclic nucleotide signals and novel molecular target for movement disorders. Eur. J. Pharmacol., [Epub ahead of print]. [PMID:23850946]

Singh N, Patra S. (2014) Phosphodiesterase 9: insights from protein structure and role in therapeutics. Life Sci., 106 (1-2): 1-11. [PMID:24746902]

* Steegborn C. (2014) Structure, mechanism, and regulation of soluble adenylyl cyclases - similarities and differences to transmembrane adenylyl cyclases. Biochim. Biophys. Acta, 1842 (12 Pt B): 2535-47. [PMID:25193033]

Vatner SF, Park M, Yan L, Lee GJ, Lai L, Iwatsubo K, Ishikawa Y, Pessin J, Vatner DE. (2013) Adenylyl cyclase type 5 in cardiac disease, metabolism, and aging. Am. J. Physiol. Heart Circ. Physiol., 305 (1): H1-8. [PMID:23624627]

Zhang M, Kass DA. (2011) Phosphodiesterases and cardiac cGMP: evolving roles and controversies. Trends Pharmacol. Sci., 32 (6): 360-5. [PMID:21477871]

How to cite this family page

Database page citation:

Cyclic nucleotide turnover/signalling. Accessed on 12/07/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=241.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Kelly E, Marrion N, Peters JA, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Southan C, Davies JA and CGTP Collaborators (2015) The Concise Guide to PHARMACOLOGY 2015/16: Enzymes. Br J Pharmacol. 172: 6024-6109.