Phosphodiesterase: Difference between revisions

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In [[biochemistry]], a '''phosphodiesterases''' are a "class of [[enzyme]]s that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound."<ref>{{MeSH}}</ref>
In [[biochemistry]], a '''phosphodiesterases''' (also called '''phosphoric diester dydrolases''') are a "class of [[enzyme]]s that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound."<ref>{{MeSH}}</ref>


An important function of phosphodiesterases is terminating [[signal transduction]] by the breakdown of the [[second messenger system|second messengers]] [[cyclic AMP]] and [[cyclic GMP]] by hydrolysis.
An important function of phosphodiesterases is terminating [[signal transduction]] by the breakdown of the [[second messenger system|second messengers]] [[cyclic AMP]] and [[cyclic GMP]] by hydrolysis.


==Classification==
==Classification==
[[Caffeine]] and [[theophylline]] are methylated xanthine derivatives that are nonselective phosphodiesterase inhibitors
===Cyclic Nucleotide Phosphodiesterases, Type 1 (PDE-1)===
===Cyclic Nucleotide Phosphodiesterases, Type 1 (PDE-1)===
These phosphodiesterases have additional specificity for [[cyclic GMP]].
These phosphodiesterases have additional specificity for [[cyclic GMP]].
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===Cyclic Nucleotide Phosphodiesterases, Type 3 (PDE-3)===
===Cyclic Nucleotide Phosphodiesterases, Type 3 (PDE-3)===
Inamrinone (previously named amrinone) and milrinone are inhibitors of PDE-3 and have been studied for use in the treatment of [[heart failure]].<ref name="isbn0-07-142280-3">{{cite book |author=Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred |authorlink= |editor= |others= |title=Goodman & Gilman's the pharmacological basis of therapeutics |edition=11th |language= |chapture=33. Pharmacological  Treatment of Heart Failure |publisher=McGraw-Hill |location=New York |year=2006 |origyear= |pages= |quote= |isbn=0-07-142280-3 |oclc= |doi= |url= |accessdate=}}</ref> These drugs improve cardiac contractility as well as increase vasodilation. Milrinone has significant adverse effects in [[randomized controlled trial]]s.<ref name="pmid2646536">{{cite journal |author=DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R |title=A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure |journal=N. Engl. J. Med. |volume=320 |issue=11 |pages=677–83 |year=1989 |month=March |pmid=2646536 |doi= |url= |issn=}}</ref><ref name="pmid1944425">{{cite journal |author=Packer M, Carver JR, Rodeheffer RJ, ''et al'' |title=Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group |journal=N. Engl. J. Med. |volume=325 |issue=21 |pages=1468–75 |year=1991 |month=November |pmid=1944425 |doi= |url= |issn=}}</ref>


===Cyclic Nucleotide Phosphodiesterases, Type 4 (PDE-4)===
===Cyclic Nucleotide Phosphodiesterases, Type 4 (PDE-4)===
[[Cilomilast]], and [[roflumilast]] are [[phosphodiesterase inhibitor]]s of PDE-4. These are used to treat [[chronic obstructive pulmonary disease]].<ref name="pmid21563134">{{cite journal| author=Chong J, Poole P, Leung B, Black PN| title=Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease. | journal=Cochrane Database Syst Rev | year= 2011 | volume= 5 | issue=  | pages= CD002309 | pmid=21563134 | doi=10.1002/14651858.CD002309.pub3 | pmc= | url= }} </ref>


===Cyclic Nucleotide Phosphodiesterases, Type 5 (PDE-5)===
===Cyclic Nucleotide Phosphodiesterases, Type 5 (PDE-5)===
Sildenafil, vardenafil, and tadalafil are phosphodiesterase inhibitors of PDE-5 which increase [[cyclic GMP]] levels leading to smooth muscle relaxation. These are used to treat [[erectile dysfunction]] and as well as [[pulmonary hypertension]].
[[Sildenafil]], [[vardenafil]], and [[tadalafil]] are [[phosphodiesterase inhibitor]]s of PDE-5 which increase [[cyclic GMP]] levels leading to smooth muscle relaxation. These are used to treat [[erectile dysfunction]] and as well as [[pulmonary hypertension]].


These phosphodiesterases have additional specificity for cyclic [[GMP]].
These phosphodiesterases have additional specificity for [[cyclic GMP]].


===Cyclic Nucleotide Phosphodiesterases, Type 6 (PDE-6)===
===Cyclic Nucleotide Phosphodiesterases, Type 6 (PDE-6)===
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==References==
==References==
<references/>
<references/>[[Category:Suggestion Bot Tag]]

Latest revision as of 17:01, 3 October 2024

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In biochemistry, a phosphodiesterases (also called phosphoric diester dydrolases) are a "class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound."[1]

An important function of phosphodiesterases is terminating signal transduction by the breakdown of the second messengers cyclic AMP and cyclic GMP by hydrolysis.

Classification

Caffeine and theophylline are methylated xanthine derivatives that are nonselective phosphodiesterase inhibitors

Cyclic Nucleotide Phosphodiesterases, Type 1 (PDE-1)

These phosphodiesterases have additional specificity for cyclic GMP.

Cyclic Nucleotide Phosphodiesterases, Type 2 (PDE-2)

These phosphodiesterases have additional specificity for cyclic GMP.

Cyclic Nucleotide Phosphodiesterases, Type 3 (PDE-3)

Inamrinone (previously named amrinone) and milrinone are inhibitors of PDE-3 and have been studied for use in the treatment of heart failure.[2] These drugs improve cardiac contractility as well as increase vasodilation. Milrinone has significant adverse effects in randomized controlled trials.[3][4]

Cyclic Nucleotide Phosphodiesterases, Type 4 (PDE-4)

Cilomilast, and roflumilast are phosphodiesterase inhibitors of PDE-4. These are used to treat chronic obstructive pulmonary disease.[5]

Cyclic Nucleotide Phosphodiesterases, Type 5 (PDE-5)

Sildenafil, vardenafil, and tadalafil are phosphodiesterase inhibitors of PDE-5 which increase cyclic GMP levels leading to smooth muscle relaxation. These are used to treat erectile dysfunction and as well as pulmonary hypertension.

These phosphodiesterases have additional specificity for cyclic GMP.

Cyclic Nucleotide Phosphodiesterases, Type 6 (PDE-6)

These phosphodiesterases have additional specificity for cyclic GMP.

Cyclic Nucleotide Phosphodiesterases, Type 7 (PDE-7)

References

  1. Anonymous (2024), Phosphodiesterase (English). Medical Subject Headings. U.S. National Library of Medicine.
  2. Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Lazo, John S.; Gilman, Alfred (2006). Goodman & Gilman's the pharmacological basis of therapeutics, 11th. New York: McGraw-Hill. ISBN 0-07-142280-3. 
  3. DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R (March 1989). "A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure". N. Engl. J. Med. 320 (11): 677–83. PMID 2646536[e]
  4. Packer M, Carver JR, Rodeheffer RJ, et al (November 1991). "Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group". N. Engl. J. Med. 325 (21): 1468–75. PMID 1944425[e]
  5. Chong J, Poole P, Leung B, Black PN (2011). "Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease.". Cochrane Database Syst Rev 5: CD002309. DOI:10.1002/14651858.CD002309.pub3. PMID 21563134. Research Blogging.