Effects of histamine and histamine antagonists on the uptake and release of catecholamines and 5-HT in brain synaptosomes.
The effect of histamine and histamine antagonists on the uptake and release of monoamines was studied using rat brain synaptosomes. For uptake experiments, P2-synaptosome fractions were incubated in buffer for 2 min in the presence of tritiated dopamine, noradrenaline or 5-hydroxytryptamine (5-HT) and the inhibitor studied. Only an /H1-antagonist mepyramine (pyrilamine) inhibited monoamine uptake at reasonable concentrations. For release experiments, preloaded synaptosomes were incubated with the substanances to be studied for 2 or 5 min in buffer, and the decrease in radio-activity assayed and compared with synaptosomes incubated with the solvent. Only histamine caused some release, but the concentration range necessary to cause a similar level of release was at least one hundred times greater than that of tyramine. Hence it is unlikely that H2-antagonists would exert their pharmacological effects in the central nervous system by inhibiting monoamine uptake or by causing a tyramine-like releasing effect. Also histamine is necessary at very high concentrations before such secondary effects are likely.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D006633:Histamine Antagonists; D012701:Serotonin; D006632:Histamine; D011738:Pyrilamine; D004298:Dopamine; D009638:Norepinephrine