Cross-talk between adenosine and the oxatriazole derivative GEA 3175 in platelets
2005 (English)In: European Journal of Pharmacology, ISSN 0014-2999, E-ISSN 1879-0712, Vol. 517, no 3, 149-157 p.Article in journal (Refereed) Published
We examined the interplay between adenosine and the nitric oxide (NO)-containing oxatriazole derivative GEA 3175 in human platelets. The importance of cyclic guanosine 3′5′-monophosphate (cGMP)-inhibited phosphodiesterases (PDEs) was elucidated by treating the platelets with adenosine combined with either GEA 3175 or the PDE3-inhibitor milrinone. The drug combinations provoked similar cyclic adenosine 3′5′-monophosphate (cAMP) responses. On the contrary, cGMP levels were increased only in GEA 3175-treated platelets. Both drug combinations reduced P-selectin exposure, platelet adhesion and fibrinogen-binding. However, adenosine together with GEA 3175 was more effective in inhibiting platelet aggregation and ATP release. Thrombin-induced rises in cytosolic Ca2+ were suppressed by the two drug combinations. Adenosine administered with GEA 3175 was, however, more effective in reducing Ca2+ influx.
In conclusion, the interaction between adenosine and GEA 3175 involves cGMP-mediated inhibition of PDE3. The results also imply that inhibition of Ca2+ influx represent another cGMP-specific mechanism that enhances the effect of adenosine.
Place, publisher, year, edition, pages
2005. Vol. 517, no 3, 149-157 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-30677DOI: 10.1016/j.ejphar.2005.05.019Local ID: 16282OAI: oai:DiVA.org:liu-30677DiVA: diva2:251500