Increased cell-cell adhesion, a novel effect of R-(-)-deprenyl.
The neuroprotective effect of the antiparkinsonian monoamine oxidase (MAO)-B inhibitor, R-(-)-deprenyl has been under investigation for years. Cytoskeleton, a main component of cell adhesion, is involved in the development of R-(-)-deprenyl-responsive diseases, the effect of the drug on cell adhesion, however, is not known. We examined the effect of R-(-)-deprenyl on cell-cell adhesion of neuronal and non-neuronal cells. R-(-)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell-cell adhesion of PC12 and NIH3T3 cells at concentrations lower than those required for MAO-B inhibition, while S-(+)-deprenyl was not effective. This acitvity of R-(-)-deprenyl was not prevented by the cytochrome P-450 inhibitor, SKF525A, while deprenyl-N-oxide, a newly described metabolite, also induced an increase in cell-cell adhesion. The effect of R-(-)-deprenyl was not reversible during a 24-hour recovery period. In summary, we described a new, MAO-B independent effect of R-(-)-deprenyl on cell-cell adhesion which can contribute to its neuroprotective function.
Jenei
V
V
Institute of Biomolecular Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary. veronika@chemres.hu
Zor
K
K
Magyar
K
K
Jakus
J
J
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D041681:NIH 3T3 Cells; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D011335:Proadifen / Q000494:pharmacology; D051381:Rats; D012642:Selegiline / Q000031:analogs & derivatives / Q000494:pharmacology*
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; C484174:deprenyl-N-oxide; D012642:Selegiline; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen