Effect of cAMP and cGMP on endothelin-stimulated tyrosine phosphorylation in rabbit platelets.
Activation of platelets by different agents results in the increased tyrosine phosphorylation of several substrate proteins. Thus, the effect of endothelin-1 on the stimulation of tyrosine phosphorylation in rabbit platelets can be inhibited by preincubation with forskolin, which increase the cAMP level. However, incubations of platelets with 8-Bromo-cGMP showed lower inhibitory effect. Forskolin produced a dose-dependent inhibition on three different protein substrates, with an IC50 of approximately 12.8, 4.0 and 8.0 microM in the three molecular mass ranges of 50, 60 and 100-200 kDa, respectively. These results show that the 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 some molecular mass ranges of tyrosine phosphorylated proteins.
Catalán
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RE
Departamento de Biología Molecular, CSICUAM Universidad Autónoma de Madrid, Spain.
Martínez
A M
AM
Gargiulo
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L
Liras
A
A
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000008:administration & dosage / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D006152:Cyclic GMP / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000494:pharmacology*; D008970:Molecular Weight; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000097:blood*; D011817:Rabbits; D015398:Signal Transduction
D016232:Endothelins; D005576:Colforsin; D019000:Phosphotyrosine; C016276:8-bromocyclic GMP; D000242:Cyclic AMP; D006152:Cyclic GMP