Autoinhibition of histamine synthesis mediated by presynaptic H3-receptors.

摘要: The regulation of histamine synthesis was studied on rat brain slices or synaptosomes labeled with L-[3H]histidine. Depolarization by increased extracellular K+ concentration enhanced about twofold the [3H]histamine formation in cerebral cortex. This stimulation also observed, although to a lesser extent, from cortex and posterior hypothalamus where most histaminergic cell-bodies are located, suggesting that it may occur nerve endings as well perikarya. In presence exogenous increasing concentrations K+-induced progressively reduced up 60-70%. effect appears be receptor-mediated shown its saturable character, high pharmacological specificity competitive reversal antagonists. EC50 value for reduction (0.34 +/- 0.03 microM) similar release inhibition known mediated H3-receptors. addition, whereas mepyramine tiotidine, two potent antagonists at H1- H2-receptors, respectively, were poorly effective, H3-receptor burimamide impromidine reversed an apparently manner. These effects observed cortical synaptosomes. Furthermore, even absence added histamine, depolarization-induced synthesis, indicating participation released endogenous control process. potencies those these agents presynaptic autoreceptors controlling release. It is concluded H3-receptors not only but level also, presumably, A relationship between regulatory processes, possibly via intracellular calcium, seems likely remains investigated molecular level.