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Thus phosphorylation of PDE5 and binding of cGMP to the noncatalytic sites mediate negative feedback regulation of the cGMP pathway. Binding of cGMP to the allosteric site further stimulates enzymatic activity. Phosphodiesterase 5 (PDE5) is the predominant phosphodiesterase in the corpus cavernosum.



Nerves and endothelial cells directly release nitric oxide in the p***s, where it stimulates guanylyl cyclase to produce cGMP and lowers intracellular calcium levels. PDE5 protein was found in the cortex, hippocampus, and cerebellum at a concentration of 7.15, 5.08, and 10.29 ng/g of brain tissue, respectively (3 samples in each group; error bars are standard error). A) PDE5 mRNA was detected by qPCR in human cortex using 3 different primers (see Methods), against the 3'UTR region (each primer shows the average for 3 samples; error bars are standard error).



PDE5 exists in human brain tissue. Barros-Minones L , Martin-de-Saavedra D , Perez-Alvarez S , Orejana L , Suquia V , Goni-Allo B , Hervias I , Lopez MG , Jordan J , Aguirre N , Puerta E (2013) Inhibition of calpain-regulated p35/cdk5 plays a central role in Fildena-induced protection against chemical hypoxia produced by malonate. Patil CS , Singh VP , Kulkarni SK (2006) Modulatory effect of Fildena in diabetes and electroconvulsive shock-induced cognitive dysfunction in rats.



Devan BD , Pistell PJ , Daffin LW Jr , Nelson CM , Duffy KB , Bowker JL , Bharati IS , Sierra-Mercado D , Spangler EL , Ingram DK (2007) Fildena citrate attenuates a complex maze impairment induced by intracerebroventricular infusion of the NOS inhibitor Nomega-nitro-L-arginine methyl ester. Puzzo D , Staniszewski A , Deng SX , Privitera L , Leznik E , Liu S , Zhang H , Feng Y , Palmeri A , Landry DW , Arancio (2009) Phosphodiesterase 5 inhibition improves synaptic function, memory, and amyloid-beta load in an Alzheimer's disease mouse model. Roustit M , Hellmann M , Cracowski C , Blaise S , Cracowski JL (2012) Fildena increases digital skin blood flow during all phases of local cooling in primary Raynaud's phenomenon.



Devan BD , Pistell PJ , Duffy KB , Kelley-Bell B , Spangler EL , Ingram DK (2014) Phosphodiesterase inhibition facilitates cognitive restoration in rodent models of age-related memory decline. Lakics V , Karran EH , Boess FG (2010) Quantitative comparison of phosphodiesterase mRNA distribution in human brain and peripheral tissues. Kotera J , Yanaka N , Fujishige K , Imai Y , Akatsuka H , Ishizuka T , Kawashima K , Omori K (1997) Expression of rat cGMP-binding cGMP-specific phosphodiesterase mRNA in Purkinje cell layers during postnatal neuronal development.



Van Staveren WC , Steinbusch HW , Markerink-Van Ittersum M , Repaske DR , Goy MF , Kotera J , Omori K , Beavo JA , De Vente J (2003) mRNA expression patterns of the cGMP-hydrolyzing phosphodiesterases types 2, 5, and 9 during development of the rat brain.

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