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dc.contributor.authorAronsen, Lena
dc.contributor.authorØrvoll, Elin Peggy Hanne Øien
dc.contributor.authorLyså, Roy Andre
dc.contributor.authorRavna, Aina Westrheim
dc.contributor.authorSager, Georg
dc.date.accessioned2022-07-01T08:12:10Z
dc.date.available2022-07-01T08:12:10Z
dc.date.issued2014-11-07
dc.description.abstractIntracellular cyclic nucleotides are eliminated by phosphodiesterases (PDEs) and by ATP Binding cassette transporters such as ABCC4 and ABCC5. PDE5 and ABCC5 have similar affinity for cGMP whereas ABCC5 has much higher affinity for cGMP compared with cAMP. Since the substrate (cGMP) is identical for these two eliminatory processes it is conceivable that various PDE inhibitors also modulate ABCC5-transport. Cyclic GMP is also transported by ABBC4 but the affinity is much lower with a K<sub>m</sub> 50–100 times higher than for that of ABBCC5. The present study aimed to determine K<sub>i</sub>-values for specific or relative specific PDE5 inhibitors (vardenafil, tadalafil, zaprinast and dipyridamole) and the non-specific PDE inhibitors (IBMX, caffeine and theophylline) for ABCC5 andABCC4 transport. The transport of [<sup>3</sup> H]-cGMP (2 &#956M) was concentration-dependently inhibited with the following K<sub>i</sub>-values: vardenafil (0.62 &#956M), tadalafil (14.1 &#956M), zaprinast (0.68 &#956M) and dipyridamole (1.2 &#956M), IBMX (10 &#956M), caffeine (48 &#956M) and theophylline (69 &#956M). The K<sub>i</sub>-values for the inhibition of the [<sup>3</sup> H]-cAMP (2 &#956M) transport were: vardenafil (3.4 &#956M), tadalafil (194 &#956M), zaprinast (2.8 &#956M), dipyridamole (5.5 &#956M), IBMX (16 &#956M), caffeine (41 &#956M) and theophylline (85 &#956M). The specificity for ABCC5 we defined as ratio between K<sub>i</sub>-values for inhibition of [<sup>3</sup> H]-cGMP and [<sup>3</sup> H]-cAMP transport. Tadalafil showed the highest specificity (K<sub>i</sub>-ratio: 0.073) and caffeine the lowest (K<sub>i</sub>-ratio: 1.2).en_US
dc.identifier.citationAronsen L, Ørvoll ephØ, Lyså RA, Ravna aw, Sager gs. Modulation of high affinity ATP-dependent cyclic nucleotide transporters by specific and non-specific cyclic nucleotide phosphodiesterase inhibitors. European Journal of Pharmacology. 2014;745:249-253en_US
dc.identifier.cristinIDFRIDAID 1196772
dc.identifier.doi10.1016/j.ejphar.2014.10.051
dc.identifier.issn0014-2999
dc.identifier.issn1879-0712
dc.identifier.urihttps://hdl.handle.net/10037/25698
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalEuropean Journal of Pharmacology
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2014 The Author(s)en_US
dc.titleModulation of high affinity ATP-dependent cyclic nucleotide transporters by specific and non-specific cyclic nucleotide phosphodiesterase inhibitorsen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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