Identification of cytosolic phosphodiesterases in the erythrocyte: A possible role for PDE5

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dc.contributor.authorAdderley, Shaquria P.
dc.contributor.authorThuet, Kelly M.
dc.contributor.authorSridharan, Meera
dc.contributor.authorBowles, Elizabeth A.
dc.contributor.authorStephenson, Alan H.
dc.contributor.authorEllsworth, Mary L.
dc.contributor.authorSprague, Randy S.
dc.date.accessioned2016-06-27T19:24:34Z
dc.date.available2016-06-27T19:24:34Z
dc.date.issued2011
dc.description.abstractBackground Within erythrocytes (RBCs), cAMP levels are regulated by phosphodiesterases (PDEs). Increases in cAMP and ATP release associated with activation of β-adrenergic receptors (βARs) and prostacyclin receptors (IPRs) are regulated by PDEs 2, 4 and PDE 3, respectively. Here we establish the presence of cytosolic PDEs in RBCs and determine a role for PDE5 in regulating levels of cGMP. Material/Methods Purified cytosolic proteins were obtained from isolated human RBCs and western analysis was performed using antibodies against PDEs 3A, 4 and 5. Rabbit RBCs were incubated with dbcGMP, a cGMP analog, to determine the effect of cGMP on cAMP levels. To determine if cGMP affects receptor-mediated increases in cAMP, rabbit RBCs were incubated with dbcGMP prior to addition of isoproterenol (ISO), a βAR receptor agonist. To demonstrate that endogenous cGMP produces the same effect, rabbit and human RBCs were incubated with SpNONOate (SpNO), a nitric oxide donor, and YC1, a direct activator of soluble guanylyl cyclase (sGC), in the absence and presence of a selective PDE5 inhibitor, zaprinast (ZAP). Results Western analysis identified PDEs 3A, 4D and 5A. dbcGMP produced a concentration dependent increase in cAMP and ISO-induced increases in cAMP were potentiated by dbcGMP. In addition, incubation with YC1 and SpNO in the presence of ZAP potentiated βAR-induced increases in cAMP. Conclusions PDEs 2, 3A and 5 are present in the cytosol of human RBCs. PDE5 activity in RBCs regulates cGMP levels. Increases in intracellular cGMP augment cAMP levels. These studies suggest a novel role for PDE5 in erythrocytes.en_US
dc.identifier.citationMedical Science Monitor : International Medical Journal of Experimental and Clinical Research; 17:5 p. CR241-CR247en_US
dc.identifier.doi10.12659/MSM.881763
dc.identifier.issn1234-1010
dc.identifier.pmidpmc3366467en_US
dc.identifier.urihttp://hdl.handle.net/10342/5791
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3366467/en_US
dc.subjectred blood cellen_US
dc.subjectcGMPen_US
dc.subjectisoproterenolen_US
dc.subjectPDE5en_US
dc.subjectzaprinasten_US
dc.titleIdentification of cytosolic phosphodiesterases in the erythrocyte: A possible role for PDE5en_US
dc.typeArticleen_US
ecu.journal.issue5en_US
ecu.journal.nameMedical Science Monitor : International Medical Journal of Experimental and Clinical Researchen_US
ecu.journal.pagesCR241-CR247en_US
ecu.journal.volume17en_US

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