Histamine-induced excitation of spontaneously active medullary neurones in the rat brain is mediated by H2-receptors : A microiontophoretic study using H1 and H2-agonists and antagonists

The effects of histamine, applied by microiontophoresis onto spontaneously-active medullary neurones were investigated in the rat. Histamine caused current-dependent excitation of these neurones, an action that is at variance with previous studies in the cat. The nature of the receptor mediating these effects was examined using a number of agonists with differing potencies at peripheral H₁- and H₂-receptors. The precursor of histamine, l-histidine and the metabolite, N-telemethylhistamine did not mimic the effects of histamine while the H₂-agonist, 4-methylhistamine caused similar but weaker excitation. The extent of excitations produced by the H₁-agonists, 2-pyridylethylamine, 2-methylhistamine and 2-thiazolylethylamine could be related to their activity at H₂-receptors. Metiamide was ineffective in antagonising responses to histamine and related agonists as was mepyramine. The H₂-antagonist ranitidine, however, proved a good antagonist of responses to histamine and the H₁- and H₂-agonists, despite an unrelated excitatory action which may be linked to inhibition of cholinesterase. It is concluded that the excitatory effects of microiontophoretically-applied histamine and the agonists on medullary neurones in the rat is probably a result of activation of H₂-receptors.