Acidic vesicles of the endo-exocytic pathways as targets for some anti-monoamine oxidase drugs.
Acidic vesicles are cytoplasmatic organelles delimited by a single lipoprotein membrane. They contain a large number of enzymes, mostly acidic hydrolases, catalysing various reactions at optimal acidic pH, capable of participating in intracellular digestion. In this paper, some anti-monoamine oxidase drugs (clorgyline, pargyline, amantadine and deprenyl), utilized as pharmacological treatment in some neurological disorders (e.g., Alzheimer's, Parkinson's etc. diseases), were tested for their ability to influence the pH of the acidic intracellular organelles with the aim of exploring their possible pharmacological action. Of the above mentioned drugs, clorgyline showed the most effective action in modifying the acidic vesicles' internal pH, followed by deprenyl, pargyline and amantadine. The effect was not ascribed to an increased proton conductance, but was most likely due to a weak base-like mechanism, in that they exhibit equilibria among species associated with H(+) ions and species lacking this association.
Dell'Antone
Paolo
P
Department of Biomedical Sciences, University of Padova, Padova, Italy.
IbnLkayat
Meryem
M
Drago
Denise
D
Zatta
Paolo
P
D000136:Acid-Base Equilibrium / Q000187:drug effects / Q000502:physiology; D000143:Acids / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D001927:Brain Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D003010:Clorgyline / Q000494:pharmacology; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration / Q000187:drug effects*; D051379:Mice; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D015388:Organelles / Q000187:drug effects / Q000201:enzymology; D010293:Pargyline / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D011522:Protons; D012642:Selegiline / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D022161:Transport Vesicles / Q000187:drug effects* / Q000201:enzymology
D000143:Acids; D008996:Monoamine Oxidase Inhibitors; D011522:Protons; D012642:Selegiline; D010293:Pargyline; D000547:Amantadine; D008995:Monoamine Oxidase; D003010:Clorgyline