Analyze Diet

Effects of indomethacin on neural and myogenic components in equine airway smooth muscle.

Abstract: Equine airway smooth muscle is innervated by vagal efferents and, in addition, displays spontaneous mechanical activity. The preparation thus appears to contain at least two discrete excitable components, the cholinergic neural elements and the smooth muscle membrane. Indomethacin (INDO), a cyclooxygenase (CO) inhibitor, exerts a considerable potentiation of function in this preparation. The latter may be effected indirectly, through loss of the inhibitory effect of endogenous prostaglandin E2 (PGE2) on neural acetylcholine release and through direct effects on smooth muscle of the generally antagonistic CO and lipoxygenase (LO) metabolites. The present studies were designed to assess the relative contributions of altered arachidonic acid metabolism on those respective elements. The utility of the model, in terms of distinguishing neural and myogenic components, was assessed by examining the effects of the muscarinic antagonist atropine (ATR) and the neurotoxin tetrodotoxin (TTX) on the stimulus-response (SR) relationship. The observations that TTX and ATR produced similar rightward (but not downward) shifts of the SR curve and that D-600 inhibited the TTX-insensitive responses are consistent with a selective activation of the muscle by the nerves at lower voltages and a direct stimulation of the muscle at higher voltages. INDO potentiated both the neural and myogenic components of the SR curve, effects which were sensitive to ATR and 5,8,11,14-eicosatetraynoic acid, an inhibitor of LO, and reversed by PGE2. The finding that PGE2 at low doses (10(-8) M) inhibited responses at lower voltages and that at higher concentration (10(-7) M) it shifted the SR curve right and downward suggested that neurotransmitter release is more sensitive to PGE2 inhibition than is muscle response.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1990-01-01 PubMed ID: 2105394
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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 studies the effects of indomethacin, a substance that inhibits inflammation, on the activity of vagal nerve controls and naturally occurring muscle movements in horse airway muscles. The effects were found to be affected by the function of various enzymes and chemical compounds.

Understanding The Research

The focus of the research is to understand the effects of indomethacin, a cyclooxygenase (CO) inhibitor, on equine airway smooth muscle movements. The equine airway smooth muscles that are studied here have two components:

  • Vagal efferents: These are the nerve fibers that transmit signals from a central point to the muscles.
  • Smooth muscle membrane: This is part of the muscle that can display spontaneous activity.

Role of Indomethacin

Indomethacin is found to significantly enhance the functions of the equine airway smooth muscles. This is thought to be done through:

  • Removing the inhibiting effect of naturally occurring Prostaglandin E2 on the release of neural acetylcholine.
  • Directly affecting the muscle through interaction with CO and lipoxygenase (LO), the chemical compounds commonly known as CO and LO metabolites.

Experimentation

The researchers designed various experiments to assess how changing arachidonic acid metabolism affects various elements in equine airway smooth muscles.

  • The study was used to distinguish between neural and myogenic components; myogenic meaning generated by muscle tissue itself.
  • This was done by experimenting with Atropine, a drug that blocks nerve action, and Tetrodotoxin, a strong neurotoxin.
  • The researchers observed that these substances both resulted in similar shifts in the response to stimulus but did not result in a decrease in the curve. This suggests that nerves activate the muscle at lower voltages and high voltages stimulate the muscle directly.

Conclusion

Overall, the study found that indomethacin enhances both the neural and myogenic components of the stimulus-response (SR) curve and that these effects can be impacted and reversed by other chemical compounds like PGE2.

Cite This Article

APA
Gill KK, Kroeger EA. (1990). Effects of indomethacin on neural and myogenic components in equine airway smooth muscle. J Pharmacol Exp Ther, 252(1), 358-364.

Publication

ISSN: 0022-3565
NlmUniqueID: 0376362
Country: United States
Language: English
Volume: 252
Issue: 1
Pages: 358-364

Researcher Affiliations

Gill, K K
  • Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Kroeger, E A

    MeSH Terms

    • 5,8,11,14-Eicosatetraynoic Acid / pharmacology
    • Acetylcholine / metabolism
    • Animals
    • Atropine / pharmacology
    • Dinoprostone / pharmacology
    • Horses
    • In Vitro Techniques
    • Indomethacin / pharmacology
    • Lipoxygenase / physiology
    • Muscle Contraction / drug effects
    • Prostaglandin-Endoperoxide Synthases / physiology
    • Tetrodotoxin / pharmacology
    • Trachea / drug effects
    • Trachea / physiology

    Citations

    This article has been cited 0 times.