EFFECT OF CAMP AND CGMP ON ENDOTHELIN-STIMULATED TYROSINE PHOSPHORYLATION IN RABBIT PLATELETS

Activation of platelets by different agents results in the increased t yrosine phosphorylation of several substrate proteins. Thus, the effec t of endothelin-l on the stimulation of tyrosine phosphorylation in ra bbit platelets can be inhibited by preincubation with forskolin, which increase the cAMP level. However, incubations of platelets with 8-Bro mo-cGMP showed lower inhibitory effect. Forskolin produced a dose-depe ndent inhibition on three different protein substrates, with an IC50 o f approximately 12.8, 4.0 and 8.0 mu M in the three molecular mass ran ges of 50, 60 and 100-200 kDa, respectively. These results show that t he endothelin-stimulated tyrosine phosphorylation in rabbit platelets can be regulated by a novel pathway of platelet signal transduction in which the cAMP level could be more relevantly involved than cGMP in s ome molecular mass ranges of tyrosine phosphorylated proteins. (C) 199 5 Academic Press. Inc.