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Pflügers Archiv

, Volume 445, Issue 5, pp 570–576 | Cite as

Histaminergic modulation of the intact respiratory network of adult mice

  •  M. Dutschmann
  •  A. Bischoff
  •  D. Büsselberg
  •  D. Richter
Integrative Neurophysiology

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.

Respiration Hypoxia Neuromodulation H-1 receptor Transmitter release 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  •  M. Dutschmann
    • 1
  •  A. Bischoff
    • 1
  •  D. Büsselberg
    • 1
  •  D. Richter
    • 1
  1. 1.Georg-August-Universität Göttingen, Institut für Neuro- und Sinnesphysiologie, Humboldtallee 23, 37073 Göttingen, Germany

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