title: Modulation of the megakaryoblastic Dami cell line differentiation by phosphodiesterase inhibitors and imidazo[1,2-a]pyrazine derivatives.
abstract: Phosphodiesterase inhibitors have been shown to modulate cell differentiation. We have previously shown that a series of imidazo[1,2-a]pyrazine derivatives displayed inhibitory effects on phosphodiesterase isoenzymes types III. IV and V isolated from Dami cells and on Dami cell growth. In the present study we have investigated the effect of these derivatives on the expression of two differentiation markers, glycoproteins Ib and IIb/IIIa of the human megakaryoblastic leukaemic Dami cell line in comparison to those elicited by 3-isobutyl-1-methylxanthine and selective phosphodiesterase inhibitors of types 1 (8-methoxymetyl-1-methyl-3-(2-methylpropyl) xanthine), III (Milrinone), IV (RO-201724) and V (Zaprinast). Imidazo[1,2-a]pyrazine derivatives, 3-isobutyl-1-methylxanthine and selective phosphodiesterase inhibitors, except 8-methoxymethyl-1-methyl-3-(2-methylpropyl) xanthine, decreased glycoprotein Ib expression. SCA40, SCA41, SCA44 and 3-isobutyl-1-methylxanthine-but not the other compounds affected the expression of glycoprotein IIb/IIIa in a positive manner. The effects of imidazo[1,2-a]pyrazine derivatives on glycoprotein expression appeared to be related to their phosphodiesterase inhibitory potency.
authors.affiliation: INSERM U.300, Faculty de Pharmacy, Montpellier, France.
authors.forename: K
authors.initials: K
authors.lastname: Zurbonsen
authors.forename: A
authors.initials: A
authors.lastname: Michel
authors.forename: D
authors.initials: D
authors.lastname: Vittet
authors.forename: P A
authors.initials: PA
authors.lastname: Bonnet
authors.forename: C
authors.initials: C
authors.lastname: Chevillard
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D005434:Flow Cytometry; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007947:Leukemia, Megakaryoblastic, Acute / Q000201:enzymology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*
chemical_list: D006023:Glycoproteins; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; C016276:8-bromocyclic GMP; D006152:Cyclic GMP