Activation of PDE2 and PDE5 by specific GAF ligands: delayed activation of PDE5
نویسندگان
چکیده
منابع مشابه
Direct activation of PDE5 by cGMP
In platelets, the nitric oxide (NO)-induced cGMP response is indicative of a highly regulated interplay of cGMP formation and cGMP degradation. Recently, we showed that within the NO-induced cGMP response in human platelets, activation and phosphorylation of phosphodiesterase type 5 (PDE5) occurred. Here, we identify cyclic GMP-dependent protein kinase I as the kinase responsible for the NO-ind...
متن کاملModeling and mutational analysis of the GAF domain of the cGMP-binding, cGMP-specific phosphodiesterase, PDE5.
The GAFa domain of the cGMP-binding, cGMP-specific phosphodiesterase (PDE5A) was modeled on the crystal structure of PDE2A GAF domain and residues involved in cGMP binding identified. Tandem GAFa and GAFb domains of PDE5A, expressed in Escherichia coli, bound cGMP (K(d) 27 nM). Mutation of aspartate-299 in GAFa, suggested earlier to be critical for cGMP binding, did not abrogate cGMP binding, b...
متن کاملDirect activation of PDE5 by cGMP: long-term effects within NO/cGMP signaling
n platelets, the nitric oxide (NO)–induced cGMP response is indicative of a highly regulated interplay of cGMP formation and cGMP degradation. Recently, we showed that within the NO-induced cGMP response in human platelets, activation and phosphorylation of phosphodiesterase type 5 (PDE5) occurred. Here, we identify cyclic GMP-dependent protein kinase I as the kinase responsible for the NO-indu...
متن کاملConversion of phosphodiesterase-5 (PDE5) catalytic site to higher affinity by PDE5 inhibitors.
Phosphodiesterase-5 (PDE5) specifically hydrolyzes cGMP, thereby contributing to modulation of intracellular levels of this nucleotide. In the present study, preincubation with cGMP increased PDE5 catalytic activity for cGMP degradation, and it converted the PDE5 catalytic site to a form that was more potently inhibited by each of the three PDE5 catalytic site-specific inhibitors: sildenafil, v...
متن کاملInhibition of type 5 phosphodiesterase counteracts β2-adrenergic signalling in beating cardiomyocytes.
AIMS Compartmentalization of cAMP and PKA activity in cardiac muscle cells plays a key role in maintaining basal and enhanced contractility stimulated by sympathetic nerve activity. In cardiomyocytes, activation of adrenergic receptor increases cAMP production, which is countered by the hydrolytic activity of selective phosphodiesterases (PDEs). The intracellular regional dynamics of cAMP produ...
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ژورنال
عنوان ژورنال: British Journal of Pharmacology
سال: 2010
ISSN: 0007-1188
DOI: 10.1111/j.1476-5381.2010.00977.x