Modulation of acetylcholine, capsaicin and substance P effects by histamine H3 receptors in isolated perfused rabbit lungs

Eur J Pharmacol. 1995 Apr 24;277(2-3):243-50. doi: 10.1016/0014-2999(95)00085-y.


The modulatory role of histamine H3 receptors in pulmonary oedema induced by acetylcholine, capsaicin and by exogenous substance P was investigated in isolated, ventilated rabbit lungs. Endothelial permeability was evaluated by measuring the capillary filtration coefficient (Kf,c). Acetylcholine (10(-8) to 10(-4) M), substance P (10(-10) to 10(-6) M), capsaicin (10(-4) M) and 5-hydroxytryptamine (5-HT) (10(-4) M) induced an increase in the Kf,c. Carboperamide, a novel histamine H3 receptor antagonist, induced a significant leftward shift of the concentration-response curve to acetylcholine and also enhanced the effect of capsaicin on the Kf,c, while it had no significant effect on the response to substance P and 5-HT. Imetit, a new histamine H3 receptor agonist, strongly inhibited the effects of acetylcholine and capsaicin. Imetit also strongly protected the lung against substance P effects but did not prevent the 5-HT-induced increase in the Kf,c. Carboperamide completely blocked the inhibitory effect of Imetit on the acetylcholine response. (R)-alpha-Methylhistamine, an other histamine H3 receptor agonist, had the same protective effect against acetylcholine response as Imetit. We conclude that histamine H3 receptors could protect the lung against acetylcholine- and capsaicin-induced oedema via a prejunctional modulatory effect on the C-fibres. However, since the response to exogenous substance P was also inhibited by histamine H3 receptor stimulation, the presence of such receptors at a postsynaptic level, probably on mast cells, was also suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism
  • Acetylcholine / toxicity*
  • Animals
  • Capillary Permeability / drug effects
  • Capsaicin / metabolism
  • Capsaicin / toxicity*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Endothelium / drug effects
  • Endothelium / metabolism
  • Female
  • Histamine Agonists / pharmacology
  • Histamine Antagonists / pharmacology
  • Imidazoles / pharmacology
  • In Vitro Techniques
  • Lung / drug effects
  • Male
  • Nerve Fibers / drug effects
  • Nerve Fibers / metabolism
  • Piperidines / pharmacology
  • Pulmonary Edema / chemically induced*
  • Pulmonary Edema / metabolism
  • Rabbits
  • Receptors, Histamine H3 / drug effects
  • Receptors, Histamine H3 / metabolism*
  • Serotonin / metabolism
  • Serotonin / toxicity
  • Substance P / metabolism
  • Substance P / toxicity*
  • Thiourea / analogs & derivatives
  • Thiourea / pharmacology


  • Histamine Agonists
  • Histamine Antagonists
  • Imidazoles
  • Piperidines
  • Receptors, Histamine H3
  • carboperamide
  • Serotonin
  • Substance P
  • imetit
  • Thiourea
  • Acetylcholine
  • Capsaicin