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.
Jones
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H
Bradley
P B
PB
Roberts
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F
D000818:Animals; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D007478:Iontophoresis; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011968:Receptors, Histamine / Q000187:drug effects*; D011969:Receptors, Histamine H1 / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000187:drug effects* / Q000502:physiology; D013268:Stimulation, Chemical
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011968:Receptors, Histamine; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine