Enhanced inhibition of the EDHF phenomenon by a phenyl methoxyalaninyl phosphoramidate derivative of dideoxyadenosine
- 1 May 2004
- journal article
- research article
- Published by Wiley in British Journal of Pharmacology
- Vol. 142 (1) , 27-30
- https://doi.org/10.1038/sj.bjp.0705782
Abstract
In rabbit arteries endogenous production of cAMP facilitates electrotonic signalling via gap junctions, thus explaining the ability of P‐site inhibitors of adenylyl cyclase to attenuate EDHF‐type responses. In the present study, we show that a lipophilic phosphoramidate pronucleotide derivative of dideoxyadenosine, 2′,3′‐ddA‐PMAPh, exhibits enhanced activity as an inhibitor of EDHF‐type smooth muscle hyperpolarizations induced by acetylcholine (ACh) compared to the parent nucleoside 2′,3′‐ddA, and that the effects of both compounds can be reversed by the cAMP phosphodiesterase inhibitor IBMX. Neither 2′,3′‐ddA nor 2′,3′‐ddA‐PMAPh depress ACh‐evoked endothelial hyperpolarization directly. Modifications in the lipophilicity of dideoxyadenosine and its direct intracellular delivery as a mononucleotide may thus enhance the ability to inhibit adenylyl cyclase and depress electrotonic signalling via myoendothelial gap junctions.British Journal of Pharmacology (2004) 142, 27–30. doi:10.1038/sj.bjp.0705782Keywords
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