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Effects of histamine and betahistine on rat medial vestibular nucleus neurones: possible mechanism of action of anti-histaminergic drugs in vertigo and motion sickness

Effects of histamine and betahistine on rat medial vestibular nucleus neurones: possible... 221 105 105 1 1 J. -J. Wang M. B. Dutia 44-131-650 6527 Department of Biology Nanjing University Nanjing China Department of Physiology Medical School Teviot Place EH8 9AG Edinburgh UK Abstract The tonic discharge of 71 medial vestibular nucleus (MVN) neurones was recorded in slices of the dorsal brainstem of young adult rats. Bath application of histamine caused a dose-related excitation in 59 of the 71 cells (83%), the remaining 12 (17%) being unresponsive. Dimaprit, a selective H 2 agonist, also caused excitation in all 20 cells tested. The histamine-induced excitation and the response to dimaprit were antagonised by the selective H 2 antagonist ranitidine, confirming that the H 2 subtype of histamine receptor is involved in mediating the effects of histamine on these cells. Triprolidine, a selective H 1 antagonist, also antagonised the excitation caused by histamine, at a concentration (0.3 μM) which left the H 2 receptor-mediated response to dimaprit unchanged. Thus the excitatory effects of histamine on MVN cells in the rat involve two components mediated through H 1 and H 2 receptor-linked mechanisms, respectively. Betahistine, a weak H 1 agonist and H 3 antagonist, had little excitatory action when applied on its own, but significantly reduced the excitation caused by histamine when the two drugs were applied together. The effects of betahistine were consistent with a partial-agonist action at H 1 receptors on MVN cells, reducing the excitatory responses to histamine presumably by occupying these receptor sites in competition with the exogenously applied neurotransmitter. This partial-agonist action of betahistine may be an important part of its mechanism of action in the symptomatic treatment of vertigo and motion sickness, since it is likely to occur not only in the MVN but also in many brain regions, including the thalamus and cortex, which express H 1 receptors and which are innervated by the hypothalamic histaminergic system. Thus the effectiveness of betahistine and other anti-H 1 drugs against motion sickness may be explained by their action in reducing the effects of the excess histamine release induced in such conditions in various brain areas, including the MVN. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Experimental Brain Research Springer Journals

Effects of histamine and betahistine on rat medial vestibular nucleus neurones: possible mechanism of action of anti-histaminergic drugs in vertigo and motion sickness

Experimental Brain Research , Volume 105 (1) – Jul 1, 1995

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References (27)

Publisher
Springer Journals
Copyright
Copyright © 1995 by Springer-Verlag
Subject
Biomedicine; Neurosciences; Neurology
ISSN
0014-4819
eISSN
1432-1106
DOI
10.1007/BF00242178
Publisher site
See Article on Publisher Site

Abstract

221 105 105 1 1 J. -J. Wang M. B. Dutia 44-131-650 6527 Department of Biology Nanjing University Nanjing China Department of Physiology Medical School Teviot Place EH8 9AG Edinburgh UK Abstract The tonic discharge of 71 medial vestibular nucleus (MVN) neurones was recorded in slices of the dorsal brainstem of young adult rats. Bath application of histamine caused a dose-related excitation in 59 of the 71 cells (83%), the remaining 12 (17%) being unresponsive. Dimaprit, a selective H 2 agonist, also caused excitation in all 20 cells tested. The histamine-induced excitation and the response to dimaprit were antagonised by the selective H 2 antagonist ranitidine, confirming that the H 2 subtype of histamine receptor is involved in mediating the effects of histamine on these cells. Triprolidine, a selective H 1 antagonist, also antagonised the excitation caused by histamine, at a concentration (0.3 μM) which left the H 2 receptor-mediated response to dimaprit unchanged. Thus the excitatory effects of histamine on MVN cells in the rat involve two components mediated through H 1 and H 2 receptor-linked mechanisms, respectively. Betahistine, a weak H 1 agonist and H 3 antagonist, had little excitatory action when applied on its own, but significantly reduced the excitation caused by histamine when the two drugs were applied together. The effects of betahistine were consistent with a partial-agonist action at H 1 receptors on MVN cells, reducing the excitatory responses to histamine presumably by occupying these receptor sites in competition with the exogenously applied neurotransmitter. This partial-agonist action of betahistine may be an important part of its mechanism of action in the symptomatic treatment of vertigo and motion sickness, since it is likely to occur not only in the MVN but also in many brain regions, including the thalamus and cortex, which express H 1 receptors and which are innervated by the hypothalamic histaminergic system. Thus the effectiveness of betahistine and other anti-H 1 drugs against motion sickness may be explained by their action in reducing the effects of the excess histamine release induced in such conditions in various brain areas, including the MVN.

Journal

Experimental Brain ResearchSpringer Journals

Published: Jul 1, 1995

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