Modulation of neuronal MAO activity, 5-HT uptake and imipramine binding by endogenous substances in dog cerebrospinal fluid.
Addition of small amounts of dog cerebrospinal fluid (CSF) inhibited both type A and type B monoamine oxidase (MAO) in dog brain mitochondria. The inhibition was competitive with 5-HT as substrate, but non-competitive with beta-phenylethylamine as substrate. Tricyclic antidepressants also exhibited competitive inhibition with type A MAO, but were non-competitive with type B MAO. The endogenous materials in CSF activate [3H]-imipramine specific, dose-dependent binding in dog brain preparations. The maximum number of binding sites (Bmax) increased, but the dissociation constant (Kd) was altered significantly in the presence of CSF. Addition of CSF induced a marked activation of uncompetitive [14C]-5-HT uptake in dog brain preparations. Moreover, there were reversibilities of the inhibition of MAO activity or of the activation of imipramine binding and 5-HT uptake by CSF substance after dilution experiment. These results indicate the possible presence of an endogenous psychotic drug-like substance in CSF.
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins; D002555:Cerebrospinal Fluid / Q000502:physiology*; D004285:Dogs; D007099:Imipramine / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D002352:Carrier Proteins; D011955:Receptors, Drug; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; C027775:imipramine receptor; D012701:Serotonin; D008995:Monoamine Oxidase; D007099:Imipramine