Cross-talk between adenosine and the oxatriazole derivative GEA 3175 in platelets

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...

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Published in:European journal of pharmacology Vol. 517; no. 3; pp. 149 - 157
Main Authors: Asplund Persson, Anna, Zalavary, Stefan, Lindström, Eva, Whiss, Per A., Bengtsson, Torbjörn, Grenegård, Magnus
Format: Journal Article
Language:English
Published: Amsterdam Elsevier B.V 11-07-2005
Elsevier
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Summary: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 Ca 2+ were suppressed by the two drug combinations. Adenosine administered with GEA 3175 was, however, more effective in reducing Ca 2+ influx. In conclusion, the interaction between adenosine and GEA 3175 involves cGMP-mediated inhibition of PDE3. The results also imply that inhibition of Ca 2+ influx represent another cGMP-specific mechanism that enhances the effect of adenosine.
ISSN:0014-2999
1879-0712
1879-0712
DOI:10.1016/j.ejphar.2005.05.019