Regulation of PAF-induced platelet responses by cyclic nucleotides

The existence of cross-talk mechanisms between the cyclic nucleotide system and other transduction systems involved in PAF-activated platelets is described in this study. A protein of 125 kDa, identified as pp125FAK, is tyrosine phosphorylated by PAF in a time- and concentration-dependent manner. The presence of a cAMP- or a cGMP-elevating agent, used alone or in combination, together with PAF diminished tyrosine phosphorylation. The sensitivity to cAMP shown by PAF-induced pp125 phosphorylation on tyrosine residues was similar to PAF-induced phosphorylation of a 47-kDa protein (pp47) on serine and threonine. In contrast, the latter was not affected in the presence of a cGMP-elevating agent, although it was able to enhance synergistically the inhibitory effect of forskolin. Data reported herein also show that pp47 phosphorylation and serotonin secretion are not closely correlated. Accordingly, sodium nitroprusside (SNP) did not have any effect on phosphorylation of pp47, but it was able to inhibit serotonin secretion when added alone, and it showed a synergistic inhibitory action with forskolin.