Histamine as a neurotransmitter: Fluorescence immunohistochemistry of its synthetic and degradative enzymes and purification of histamine receptor protein.

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Histamine neuron system in rat brain was demonstrated by the fluorescence immunohistochemistry with histidine decarboxylase, a histamine-forming enzyme, as a marker. The cell bodies exist only in the posterior hypothalamus and mammillary body as the tubelomammillary nucleus, and the axons with many varicosities were particularly dense in the hypothalamus, olfactory bulb, cerebral cortex, medial amygdaloid nucleus, med. vestibular n., and central grey matter of the midbrain and pons, and so on. Furthermore, recent extensive studies revealed the presence of nerve terminals in the spinal cord, thalamus, median eminence, posterior pituitary, med. geniculate n., superior colliculus, n. mesencephalic trigeminal nerve,retrochiasmatic area, and so on. In addition to histamine, the neuron system contained GABA, adenosine and galanin, a new peptide found in the intestine, as cotransmitters. On electron microscopic analysis, few typical synaptic formation was found in the varicosities of the neur … More on system, though they contained synaptic vesicles, suggesting the non-synaptic release of histamine. The antibody immunochemically cross-reacted with guinea-pig DOPA decarboxylase but did not with the rat enzyme, indicating that there are some close evolutional relationship among aromatic amino acid decarboxylases. Histamine N-methyltransferase, which is important in the inactivation of histamine released into the synaptic cleft, was purified from rat kidneys. The antibody raised against it showed a positive reaction toward rat kedney (proximal tubules were stained) but no reaction toward the brain. Currently, the monoclonal antibody is being obtained. Histamine <H_1> -receptor protein was solubilized by the mixture of CHAPS-Tween 60-glycerol from rat liver, which contained 100-fold higher [ <^3H> ]-mepyramine binding capacity than the brain, and purified by a series of column chromatographies. The affinity chromatography with diphenhydramine or mepyramine as a ligand seems to be promising for further purification. The molecular weight was determined to be 152 K by target size analysis. Less