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 |
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Main Authors: | , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
Amsterdam
Elsevier B.V
11-07-2005
Elsevier |
Subjects: | |
Online Access: | Get full text |
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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. |
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ISSN: | 0014-2999 1879-0712 1879-0712 |
DOI: | 10.1016/j.ejphar.2005.05.019 |