EXISTENCE OF ROLIPRAM-SENSITIVE PHOSPHODIESTERASE IN RAT MEGAKARYOCYTE

1 The effect of rolipram (ME3176) on ADP- and IP3-induced repetitive I (K(Ca)) in rat megakaryocyte was investigated by use of the nystatin p erforated patch and conventional whole-cell patch-clamp techniques. 2 The ADP-induced I(K(Ca)) was depressed by treatment with rolipram in a concentration-dependent manner. The inhibition by rolipram disappeare d after treatment with a cyclic nucleotide-dependent protein kinase in hibitor, H-8. The inhibition of I(K(Ca)) was also observed in the pres ence of cyclic AMP accumulating agents such as forskolin and isobutylm ethylxanthine (IBMX). 3 Rolipram enhanced the inhibitory action of for skolin, suggesting that rolipram facilitates the accumulation of cycli c AMP by blocking its breakdown. Similar results was obtained with ade nosine, an endogenous adenylate cyclase activator. 4 Intracellular app lication of inositol trisphosphate (IP3) induced repetitive I(K(Ca)) i n megakaryocytes. The induced I(K(Ca)) was also inhibited by rolipram and by other cyclic AMP accumulating agents. 5 It was concluded that m egakaryocytes possess rolipram-sensitive phosphodiesterase (PDE), whic h was not detected in platelets, but plays a distinct modulatory role in megakaryocytes for generating ADP-induced I(K(Ca)).