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.