The neurotrophic pyrimidine heterocyclic compound MS-818 promotes the angiogenesis induced by basic FGF.
The chorioallantoic membrane (CAM) assay is a bioassay used widely for testing angiogenic activities of compounds. In the present study, we used this assay to explore the gross and micropathological effects of 2-piperadino-6-methyl-5-oxo-5,6-dihydro (7H) pyrrolo[3,4-d] pyrimidine maleate (MS-818) in combination with basic fibroblast growth factor (bFGF). Light microscopy revealed that application of 1, 10 and 100 ng/ml bFGF to the CAM induced a concentration-dependent increase in the number of new blood vessels, whereas application of 0.01, 0.1 and 1.0 mM MS-818 did not increase angiogenesis significantly. The combinations of 10 ng/ml bFGF with 0.1, 0.1 and 1.0 mM MS-818 showed significantly greater angiogenic effects than 10 ng/ml bFGF alone. However, 1 and 100 ng/ml bFGF in combination with these concentrations of MS-818 showed no additive effects. Histologically, numerous mononuclear cells became present in the mesodermal stroma, especially around the capillaries, when MS-818 alone and with bFGF was applied to the CAM. The new vessels formed in response to MS-818 plus bFGF were smaller than those formed with bFGF alone. These results suggest that, in the CAM assay system, MS-818 promoted angiogenesis effectively when the concentration or activity of the angiogenic factor (bFGF) was potentiated by MS-818 at a real optimal level.
Yasuhara
S
S
Department of Neurosurgery, Yamaguchi University School of Medicine, Japan.
Kashiwagi
S
S
Ito
H
H
Awaya
A
A
D000482:Allantois / Q000098:blood supply; D000818:Animals; D002645:Chickens; D002823:Chorion / Q000098:blood supply; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010063:Ovum / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology*
C096499:MS 818; D011743:Pyrimidines; D016222:Fibroblast Growth Factor 2