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The veterinary quarterly1997; 19(2); 54-57; doi: 10.1080/01652176.1997.9694740

Characterization of muscarinic receptors in equine tracheal smooth muscle in vitro.

Abstract: This study was undertaken to assess the importance of muscarinic receptor subtypes in equine airway disease. Smooth muscle strips from the mid-cervical portion of the trachea of horses were placed in tissue baths and isometric contractile force was measured. Active force was measured in response to metacholine and the selective muscarinic receptor agonists McN-A-343 (M1-selective) and pilocarpine (M2-selective) in cumulative concentrations (10(-9)M through 10(-3)M), with and without preincubation with three or four concentrations of the selective muscarinic receptor antagonists pirenzepine (M1-selective), methoctramine (M2-selective), and 4-DAMP (M3-selective). The tissues contracted in response to all muscarinic agonists. The maximum responses (mean +/- sem) were 86.7 +/- 6.2 g for metacholine, 27.1 +/- 2.5 g for McN-A-343 and 37.6 +/- 3.5 g for pilocarpine. Preincubation with the selective muscarinic receptor antagonists resulted in dose-dependent rightward shifts of the concentration-effect curves for metacholine. pA2 values (means +/- sem) were 8.88 +/- 0.30 for 4-DAMP, 6.53 +/- 0.38 for methoctramine, and 6.72 +/- 0.31 for pirenzepine. Preincubation with 10(-7) M 4-DAMP resulted in a rightward shift of the concentration-effect curves for McN-A-343 and pilocarpine. These results indicate that the most important muscarinic receptor mediating contraction of equine tracheal smooth muscle is of the M3-type. Therefore relatively low concentrations of a M3-selective muscarinic receptor antagonist will inhibit acetylcholine-induced contraction of equine airway smooth muscle.
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Publication Date: 1997-06-01 PubMed ID: 9225432DOI: 10.1080/01652176.1997.9694740Google Scholar: Lookup
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  • Journal Article

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 examines the role of different types of muscarinic receptors in horse tracheal muscle contraction and its importance in equine airway diseases. It concludes that M3-type muscarinic receptors are the most important for equine tracheal muscle contraction.

Methodology

  • The researchers collected smooth muscle strips from the mid-cervical (the middle part) of the trachea (the tube that carries air in and out of the lungs) in horses.
  • The muscle strips were then placed in tissue baths where their contractile force (the ability to contract) was measured under various conditions.
  • The muscle’s reactions to metacholine, McN-A-343 (M1-selective), and pilocarpine (M2-selective), different types of muscarinic receptor agonists, were measured across a range of concentrations.
  • The experiment was repeated with pre-incubation of the muscle strips in various concentrations of different selective muscarinic receptor antagonists, including pirenzepine (M1-selective), methoctramine (M2-selective), and 4-DAMP (M3-selective).

Findings

  • The study found that the muscles contract in response to all muscarinic agonists.
  • The maximum response forces were measured at 86.7 +/- 6.2 grams for metacholine, 27.1 +/- 2.5 grams for McN-A-343, and 37.6 +/- 3.5 grams for pilocarpine.
  • Using selective muscarinic receptor antagonists led to the dose-dependent rightward shift of the concentration-effect curves for metacholine.
  • The pA2 (a measure of the effectiveness of an antagonist drug) values were highest for 4-DAMP (M3-selective), followed by pirenzepine (M1-selective), and methoctramine (M2-selective).
  • Preincubation with 10(-7) M 4-DAMP (M3-selective antagonist) resulted in a rightward shift of the concentration-effect curves for both McN-A-343 (M1-selective agonist) and pilocarpine (M2-selective agonist).

Conclusion

  • The results suggest that the M3-type muscarinic receptor is the most important in contracting equine tracheal smooth muscle. This suggests that lower concentrations of an M3-selective muscarinic receptor antagonist can inhibit acetylcholine-induced contraction of horse airway smooth muscle.
  • The findings may contribute to our understanding of equine airway diseases and guide the development of more effective treatments.

Cite This Article

APA
van Nieuwstadt RA, Henricks PA, Hajer R, van der Meer van Roomen WA, Breukink HJ, Nijkamp FP. (1997). Characterization of muscarinic receptors in equine tracheal smooth muscle in vitro. Vet Q, 19(2), 54-57. https://doi.org/10.1080/01652176.1997.9694740

Publication

The veterinary quarterly
ISSN: 0165-2176
NlmUniqueID: 7909485
Country: England
Language: English
Volume: 19
Issue: 2
Pages: 54-57

Researcher Affiliations

van Nieuwstadt, R A
  • Department of Large Animal Medicine and Nutrition, Utrecht University, The Netherlands.
Henricks, P A
    Hajer, R
      van der Meer van Roomen, W A
        Breukink, H J
          Nijkamp, F P

            MeSH Terms

            • Animals
            • Drug Interactions
            • Horses
            • In Vitro Techniques
            • Male
            • Methacholine Chloride / pharmacology
            • Muscarinic Agonists / pharmacology
            • Muscarinic Antagonists / pharmacology
            • Muscle Contraction / drug effects
            • Muscle, Smooth / drug effects
            • Pilocarpine / pharmacology
            • Receptors, Muscarinic / drug effects
            • Trachea

            Citations

            This article has been cited 6 times.
            1. Yoo EJ, Cao G, Koziol-White CJ, Ojiaku CA, Sunder K, Jude JA, Michael JV, Lam H, Pushkarsky I, Damoiseaux R, Di Carlo D, Ahn K, An SS, Penn RB, Panettieri RA Jr. Gα(12) facilitates shortening in human airway smooth muscle by modulating phosphoinositide 3-kinase-mediated activation in a RhoA-dependent manner. Br J Pharmacol 2017 Dec;174(23):4383-4395.
              doi: 10.1111/bph.14040pubmed: 28921504google scholar: lookup
            2. Shaikh N, Johnson M, Hall DA, Chung KF, Riley JH, Worsley S, Bhavsar PK. Intracellular interactions of umeclidinium and vilanterol in human airway smooth muscle. Int J Chron Obstruct Pulmon Dis 2017;12:1903-1913.
              doi: 10.2147/COPD.S134420pubmed: 28721035google scholar: lookup
            3. Gupta P, O'Mahony MS. Potential adverse effects of bronchodilators in the treatment of airways obstruction in older people: recommendations for prescribing. Drugs Aging 2008;25(5):415-43.
              doi: 10.2165/00002512-200825050-00005pubmed: 18447405google scholar: lookup
            4. Vietmeier J, Niedorf F, Bäumer W, Martin C, Deegen E, Ohnesorge B, Kietzmann M. Reactivity of equine airways--a study on precision-cut lung slices. Vet Res Commun 2007 Jul;31(5):611-9.
              doi: 10.1007/s11259-007-3501-ypubmed: 17252319google scholar: lookup
            5. Gosens R, Zaagsma J, Meurs H, Halayko AJ. Muscarinic receptor signaling in the pathophysiology of asthma and COPD. Respir Res 2006 May 9;7(1):73.
              doi: 10.1186/1465-9921-7-73pubmed: 16684353google scholar: lookup
            6. Törneke K, Ingvast-Larsson C, Boström A, Appelgren LE. Muscarinic receptors in equine airways. Vet Res Commun 2002 Dec;26(8):637-50.
              doi: 10.1023/a:1020924921676pubmed: 12507038google scholar: lookup
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