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The Journal of physiology2000; 523 Pt 1(Pt 1); 131-138; doi: 10.1111/j.1469-7793.2000.t01-3-00131.x

Signalling pathway for histamine activation of non-selective cation channels in equine tracheal myocytes.

Abstract: 1. The signalling pathway underlying histamine activation of non-selective cation channels was investigated in single equine tracheal myocytes. Application of histamine (100 microM) activated the transient calcium-activated chloride current (ICl(Ca)) and sustained, low amplitude non-selective cation current (ICat). The H1 receptor antagonist pyrilamine (10 microM) blocked activation of ICl(Ca) and ICat. Simultaneous application of histamine (100 microM) and caffeine (8 mM) during H1 receptor blockade activated ICl(Ca), but not ICat. Neither the H2 receptor antagonist cimetidine (20 microM) nor the H3 receptor antagonist thioperamide (20 microM) prevented activation of ICl(Ca) and ICat. 2. Intracellular dialysis of anti-Galphai/Galphao antibodies completely blocked activation of ICat by histamine, whereas ICl(Ca) was not affected. By contrast, anti-Galphaq/Galpha11 antibodies greatly inhibited ICl(Ca), but did not alter activation of ICat. 3. 1-Oleoyl-2-acetyl-sn-glycerol (OAG, 20-100 microM) did not induce any current or affect currents activated by histamine or methacholine (mACH). Simultaneous application of OAG and caffeine activated ICl(Ca), but not ICat, indicating that a rise in [Ca2+]i and stimulation of diacylglycerol-sensitive protein kinase C (PKC) is not sufficient to activate ICat. The phospholipase C inhibitor U73122 (2 microM) blocked histamine activation of ICl(Ca) and ICat, but simultaneous exposure of myocytes to histamine and caffeine restored both ICl(Ca) and ICat in the presence of U73122. 4. Histamine and mACH activated currents with equivalent I-V relationships. The currents activated by these agonists were not additive; following activation of ICat by mACH, histamine failed to induce an additional membrane current. Similarly, mACH did not induce an additional current after full activation of ICat by histamine. 5. We conclude that H1 histamine receptors activate ICat through coupling to Gi/Go proteins. Activation of ICat also requires intracellular calcium release, mediated by H1 receptors coupling to Gq/G11 proteins. This coupling is analogous to the activation of ICat by co-stimulation of M2 and M3 receptors.
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Publication Date: 2000-02-16 PubMed ID: 10673549PubMed Central: PMC2269777DOI: 10.1111/j.1469-7793.2000.t01-3-00131.xGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates the specific pathway linked with histamine activation of non-selective cation channels in equine tracheal myocytes. It concludes that H1 histamine receptors activate these channels through the coupling to Gi/Go proteins, and the activation also requires the intracellular release of calcium.

Research Methodology and Findings

  • The main focus of this study was the investigation process of histamine activation of non-selective cation channels in single equine tracheal myocytes.
  • Researchers used 100 microM histamine to activate the transient calcium-activated chloride current (ICl(Ca)) and the sustained, low amplitude non-selective cation current (ICat).
  • Both ICl(Ca) and ICat were blocked using H1 receptor antagonist pyrilamine (10 microM).
  • Although histamine and caffeine couldn’t activate ICat during H1 receptor blockade, they were able to activate ICl(Ca).
  • Application of anti-Galphai/Galphao antibodies entirely inhibited the histamine activation of ICat. On the other hand, anti-Galphaq/Galpha11 antibodies largely inhibited ICl(Ca), but did not alter activation of ICat.
  • In the presence of U73122, a phospholipase C inhibitor, histamine activation of ICl(Ca) and ICat were blocked. However, when myocytes were simultaneously exposed to histamine and caffeine, both currents were restored.

Conclusions of the Study

  • Histamine and mACH activated currents had equivalent I-V relationships, indicating these agonists operate similarly, their activations were not additive.
  • H1 histamine receptors are implicated in the activation of ICat through coupling to Gi/Go proteins. Moreover, this activation also demands intracellular calcium release, which is steered by H1 receptors coupling to Gq/G11 proteins.
  • The study stated that this activated coupling bears resemblance to the activation of ICat by co-stimulation of M2 and M3 receptors.

Cite This Article

APA
Wang YX, Kotlikoff MI. (2000). Signalling pathway for histamine activation of non-selective cation channels in equine tracheal myocytes. J Physiol, 523 Pt 1(Pt 1), 131-138. https://doi.org/10.1111/j.1469-7793.2000.t01-3-00131.x

Publication

The Journal of physiology
ISSN: 0022-3751
NlmUniqueID: 0266262
Country: England
Language: English
Volume: 523 Pt 1
Issue: Pt 1
Pages: 131-138

Researcher Affiliations

Wang, Y X
  • Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104-6046, USA.
Kotlikoff, M I

    MeSH Terms

    • Animals
    • Calcium / physiology
    • Cations / metabolism
    • Chloride Channels / physiology
    • Diglycerides / biosynthesis
    • Electric Conductivity
    • Histamine / pharmacology
    • Histamine / physiology
    • Horses
    • Ion Channels / drug effects
    • Ion Channels / physiology
    • Methacholine Chloride / pharmacology
    • Muscle, Smooth / cytology
    • Muscle, Smooth / metabolism
    • Receptors, Histamine H1 / physiology
    • Signal Transduction / physiology
    • Trachea / cytology
    • Trachea / metabolism

    Grant Funding

    • R01 HL045239 / NHLBI NIH HHS
    • HL 41084 / NHLBI NIH HHS
    • HL 45239 / NHLBI NIH HHS

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    Citations

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