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Overview of Cyclic Nucleotide Phosphodiesterase Isoenzyme: a Review Article
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M Saberi karimian   , M Parizad , S Samadi , D Alamdari , D Mosavi nasab , N Ahmadi * 1, M Hadavi |
| 1- , nayebalia@sbmu.ac.ir |
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Abstract: (30034 Views) |
| Phosphodiesterase enzymes (PDEs) cata-lyze selectively the hydrolysis of the cAMP and cGMP cyclic nucleotides. Nowadays, 53 isoenzymes have been identified in 11 families of Phosphodiesterase enzymes. The enzymes control the accesibilty of sec-ond messengers to their intracellular effectors. PDEs display variation in struct-ure, kinetic characteristics, regulatory mec-hanisemes, inhibitor sensivity, and response to special factors as well as the affinity to substrate (cAMP and cGMP). Each PDE family not only have their own specific sub-strates and regulatory characteristics, but also display their own specific tissue, cellu-lar and subcellular expression patterns and consequently participate in different signal transduction pathways.
The importance of physiological effects of cAMP and PDE inhibitors was clarified in 1950s. The cAMP nucleotide was introdu-ced as a second messenger that mediating many cellular impacts of nourological tran-smitters and hormones. The second messen-ger, cGMP, was discovered a few years later in rat urine. Recent studies have dem-onstrated that phosphodiesterase enzymes can be inhibited nonselectively by IBMX (3-isobutyl-1-methyl-xantine) which increa-seng cAMP level and the IC50 for all PDEs were reported o be in the range of milim-olar, with the exception for PDE8A, PDE8-B and PDE9A.
Obviously, the clinical usage of different PDE inhibitors has been known in recent years. Among various PDE inhibitors some compounds were not acceptable for the sake of their undesirable side effects. Overlap
ping enzyme activity, drug sensivity and tissue distribution of phosphodiesterases comprised their side effects. Further invest-ingation of PDEs in order to identifiy new PDE inhibitors would lead to improve their therapeutic effects and reduce their undesir-able side effects. |
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| Keywords: cyclic nucleotide phosphodiesterase, phosphodiesterase inhibitors |
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Full-Text [PDF 679 kb]
(9035 Downloads)
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Type of Study: Research |
Subject:
Internal operations( nursing )
Received: 2013/10/14 | Accepted: 2013/10/15 | Published: 2013/10/15
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