Histaminergic modulation of the intact respiratory network of adult mice

M. Dutschmann, A. M. Bischoff, Dietrich Busselberg, D. W. Richter

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Histaminergic modulation of neuronal activity in the respiratory network was investigated under normoxic and hypoxic conditions in the working heart-brainstem preparation of adult mice. Systemic application of histamine, as well as the H-1 and H-3 receptor agonists 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT) and imetit, 0.5-10 μM, significantly increased the frequency of respiratory burst discharges. Dimaprit, an H-2 receptor agonist, had no effect on respiratory activity. To test for ongoing histaminergic modulation we applied the histamine receptor antagonists pyrilamine (H-1); cimetidine (H-2) and thioperamide (H-3), each 0.5-10 μM. Only the H-1 receptor antagonist had significant effects, viz. reduction of respiratory frequency and depression of burst amplitude. Underlying effects of histamine receptor activation were identified at the cellular level. Intracellular recordings showed that histamine mediated an increase in synaptic drive potentials in inspiratory neurones while augmentation of inhibitory and excitatory synaptic activity was observed in expiratory neurones. The augmented synaptic depolarisation of inspiratory neurones was blocked by the H-1 receptor antagonist. Histaminergic modulation is also involved in the hypoxic response of the respiratory network. Blockade of H-1 receptors significantly attenuated secondary depression of the biphasic hypoxic responses, while hypoxic augmentation was not affected. We conclude that histamine is a functional neuromodulator, which is tonically active in the respiratory network and is activated further during hypoxia. The data indicate that histaminergic neuromodulation acts predominantly via H-1 receptors.

Original languageEnglish
Pages (from-to)570-576
Number of pages7
JournalPflugers Archiv European Journal of Physiology
Volume445
Issue number5
Publication statusPublished - 1 Feb 2003
Externally publishedYes

Fingerprint

Histamine
Neurons
Histamine Receptors
thioperamide
Modulation
Dimaprit
Pyrilamine
Synaptic Potentials
Respiratory Burst
Histamine Antagonists
Cimetidine
Depolarization
Respiratory Insufficiency
Brain Stem
Neurotransmitter Agents
Chemical activation
imetit
Isolated Heart Preparation
Hypoxia

Keywords

  • H-1 receptor
  • Hypoxia
  • Neuromodulation
  • Respiration
  • Transmitter release

ASJC Scopus subject areas

  • Physiology

Cite this

Histaminergic modulation of the intact respiratory network of adult mice. / Dutschmann, M.; Bischoff, A. M.; Busselberg, Dietrich; Richter, D. W.

In: Pflugers Archiv European Journal of Physiology, Vol. 445, No. 5, 01.02.2003, p. 570-576.

Research output: Contribution to journalArticle

Dutschmann, M. ; Bischoff, A. M. ; Busselberg, Dietrich ; Richter, D. W. / Histaminergic modulation of the intact respiratory network of adult mice. In: Pflugers Archiv European Journal of Physiology. 2003 ; Vol. 445, No. 5. pp. 570-576.
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