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

Asplund Persson, Anna,1966-Linköpings universitet,Farmakologi,Hälsouniversitetet (author)

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.

Zalavary, StefanLinköpings universitet,Hälsouniversitetet(Swepub:liu)steza78 (author)
Lindström, Eva,1961-Linköpings universitet,Farmakologi,Hälsouniversitetet(Swepub:liu)evali73 (author)
Whiss, Per A,1966-Linköpings universitet,Farmakologi,Hälsouniversitetet(Swepub:liu)perwh53 (author)
Bengtsson, Torbjörn,1955-Linköpings universitet,Farmakologi,Hälsouniversitetet(Swepub:liu)torbe62 (author)
Grenegård, Magnus,1963-Linköpings universitet,Farmakologi,Hälsouniversitetet(Swepub:liu)maggr06 (author)
Linköpings universitetFarmakologi (creator_code:org_t)

In:European Journal of Pharmacology: Elsevier BV517:3, s. 149-1570014-29991879-0712

By the author/editor: Asplund Persson, ...; Zalavary, Stefan; Lindström, Eva, ...; Whiss, Per A, 19 ...; Bengtsson, Torbj ...; Grenegård, Magnu ...

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