Regulation of inducible nitric oxide synthase by cAMP-elevating phospho-diesterase inhibitors
2003
Тип документа:
Чланак у часопису (Објављена верзија)
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© 2003 by Bentham Science Publishers Ltd.
Метаподаци
Приказ свих података о документуАпстракт:
Among the numerous genes controlled by cyclic adenosine monophosphate (cAMP)/protein kinase A signalling machinery is the gene encoding the inducible nitric oxide synthase (iNOS), an enzyme catalyzing the synthesis of a highly reactive free radical nitric oxide (NO). While being a major microbicidal and tumoricidal molecule, iNOS-derived NO has also been implicated in tissue destruction, as well as in regulation of inflammatory/immune cell function in various disorders associated with excessive inflammation. A feasible way for cAMP-dependent therapeutic control of inflammation, including iNOS-mediated NO synthesis, could involve the administration of drugs that block the enzymatic activity of cAMP-degrading phosphodiesterases (PDE). Indeed, cAMP-elevating PDE inhibitors can influence iNOS activation in different cell types in vitro, and their potent anti-inflammatory effects in experimental disease models and clinical studies were frequently accompanied with profound modulation of NO production. A set of conflicting data has been generated over the years, ranging from strong suppression to marked enhancement of NO release by cAMP-increasing PDE inhibitors, depending on cell-type, iNOS stimuli, and/or the agents used. The present review summarizes the data on iNOS modulation by cAMP-elevating PDE inhibitors and possible mechanisms behind it, speculating on its contribution to the therapeutic effects of these drugs.
Кључне речи:
cAMP; iNOS; nitric oxide; phosphodiesterase; inflammationИзвор:
Current Drug Targets - Inflammation and Allergy, 2003, 2, 1, 63-67Финансирање / пројекти:
- Ministry of Science and Technology, Republic of Serbia, Yugoslavia