MODULATION OF THE MEGAKARYOBLASTIC DAMI CELL-LINE DIFFERENTIATION BY PHOSPHODIESTERASE INHIBITORS AND IMIDAZO[1,2-A]PYRAZINE DERIVATIVES

Phosphodiesterase inhibitors have been shown to modulate cell differen tiation. We have previously shown that a series of imidazo[1,2-a]pyraz ine derivatives displayed inhibitory effects on phosphodiesterase isoe nzymes types III, IV and V isolated from Dami cells and on Dami cell g rowth. In the present study we have investigated the effect of these d erivatives on the expression of two differentiation markers, glycoprot eins Ib and IIb/IIIa of the human megakaryoblastic leukaemic Dami cell line in comparison to those elicited by 3-isobutyl-1-methylxanthine a nd selective phosphodiesterase inhibitors of types I (8-methoxymethyl- 1-methyl-3-(2-methylpropyl) xanthine), III (Milrinone), IV (RO-201724) and V (Zaprinast). Imidazo[1,2-a]pyrazine derivatives, 3-isobutyl-1-m ethylxanthine and selective phosphodiesterase inhibitors, except 8-met hoxymethyl-1-methyl-3-(2-methylpropyl) xanthine, decreased glycoprotei n Ib expression. SCA40, SCA41, SCA44 and 3-isobutyl-1-methylxanthine b ut not the other compounds affected the expression of glycoprotein IIb /IIIa in a positive manner. The effects of imidazo[1,2-a]pyrazine deri vatives on glycoprotein expression appeared to be related to their pho sphodiesterase inhibitory potency.