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Home / Equine Research Bank / Vet Res Commun / Segment-dependent expression of muscarinic acetylcholine rec...
Veterinary research communications2006; 31(2); 207-226; doi: 10.1007/s11259-006-3396-z

Segment-dependent expression of muscarinic acetylcholine receptors and G-protein coupling in the equine respiratory tract.

Abstract: Muscarinic receptors are considered to be of comparable clinical importance in chronic obstructive pulmonary disease (COPD) in equines and in humans. At present, data are scarce on the expression and distribution of probable subtypes of these receptors and their signalling pathways in airway segments, including lung parenchyma and bronchial and tracheal epithelium with the underlying smooth muscle in horses. Specific [N-methyl-3H]scopolamine chloride ([3H]NMS) binding to all three tissues was saturable and of high affinity, with KD values ranging between 1.6+/-0.7 and 1.9+/-0.3 nmol/L. [3H]NMS binding identified a higher density of total muscarinic receptors (fmol/mg protein) in the trachea (720+/-59 nmol/L) than in bronchi (438+/-48 nmol/L) or lung (22 +/- 3 nmol/L). Competitive binding studies using [3H]NMS and the unlabelled subtype-selective antagonists pirenzepine and telenzepine (M1), methoctramine and himbacine (M2), 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) (M3), tropicamide (M4) and mamba toxin (MT-3) (M4) indicated the presence of at least three muscarinic receptor subtypes in peripheral lung tissue (50:40:24-28%: M2>M3>M1), whereas in bronchus and trachea M2 subtypes (87-90%) predominated over M3 (14-22%), and M1 subtypes were lacking. No differences were found between tissues in high-affinity binding sites for carbachol in the absence (31-36%) or presence of guanosine 5'-triphosphate (GTP) (approximately 100%). Western blotting for G-protein alpha-subunits showed a much more robust expression of G(alphai1/2) in the trachea (with highest receptor density) than in the lung or bronchi, whereas G(alphas)-protein was dominantly expressed in bronchus. Concomitantly, carbachol inhibited isoproterenol- and GTP-stimulated adenylyl cyclase activity with increasing muscarinic receptor expression (trachea > bronchi > lung). We conclude that the expression and signalling pathways of muscarinic receptors in the equine respiratory tract are segment-dependent. These receptors might contribute to the pathogenesis of COPD in the horse and could provide potential drug targets for the therapeutic use of anticholinergics in this species.
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Publication Date: 2006-12-15 PubMed ID: 17180451DOI: 10.1007/s11259-006-3396-zGoogle 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.

This research studied the role and variations of muscarinic receptors, which are linked to chronic obstructive pulmonary disease (COPD), in different parts of the horse respiratory tract. A greater density of these receptors was identified in the trachea than in the bronchi or lung, pointing to the potential for targeted therapeutics in horses with COPD.

Introduction and Background

  • Muscarinic receptors play a significant role in the development and management of COPD in both humans and horses.
  • Despite their clinical significance, data regarding the distribution and subtypes of these receptors in various airway segments such as the lung parenchyma and bronchial and tracheal epithelium in horses are sparse.

Key Findings

  • The study found that the binding of [N-methyl-3H]scopolamine chloride ([3H]NMS) to the tissues of the trachea, bronchi, and lungs was significant and high-affinity.
  • The density of total muscarinic receptors was found more concentrated in the trachea than in the bronchi or lungs.
  • Further examination identified at least three muscarinic receptor subtypes in peripheral lung tissues, with different levels and predominance in the bronchus and trachea.
  • Interestingly, no M1 subtype was detected in the bronchus and trachea.

Protein Coupling and Expression

  • There was no difference observed in the high-affinity binding sites for carbachol, a muscarinic agonist, between the tissues in the presence or absence of guanosine 5′-triphosphate (GTP), a critical energy transfer molecule.
  • A Western blot test revealed higher expression of G-protein alpha-subunits (G(alphai1/2)) in the trachea than the lung or bronchi.
  • In the bronchus, the G(alphas)-protein had dominant expression.

Implications and Conclusion

  • The finding that carbachol inhibited isoproterenol- and GTP-stimulated adenylyl cyclase activity supports the importance of muscarinic receptor density in the functioning of the respiratory tract.
  • The overall findings suggest that tiered receptor expression might significantly influence the behaviour of these receptors and could contribute to the progression of COPD in horses.
  • These findings may potentially aid in the development of therapeutic anticholinergics for COPD treatment in horses by targeting these muscarinic receptors.
  • Further research is required to understand how these mechanisms function in other species and how they translate into potential therapeutic strategies.

Cite This Article

APA
Abraham G, Kottke C, Ammer H, Dhein S, Ungemach FR. (2006). Segment-dependent expression of muscarinic acetylcholine receptors and G-protein coupling in the equine respiratory tract. Vet Res Commun, 31(2), 207-226. https://doi.org/10.1007/s11259-006-3396-z

Publication

Veterinary research communications
ISSN: 0165-7380
NlmUniqueID: 8100520
Country: Switzerland
Language: English
Volume: 31
Issue: 2
Pages: 207-226

Researcher Affiliations

Abraham, G
  • Institute of Pharmacology, Pharmacy and Toxicology, Leipzig University, Leipzig.
Kottke, C
    Ammer, H
      Dhein, S
        Ungemach, F R

          MeSH Terms

          • Adenylyl Cyclases / metabolism
          • Animals
          • Binding, Competitive
          • Blotting, Western / veterinary
          • GTP-Binding Proteins / metabolism
          • Horse Diseases / drug therapy
          • Horse Diseases / metabolism
          • Horses
          • In Vitro Techniques
          • Muscarinic Agonists / pharmacology
          • Muscarinic Antagonists / pharmacology
          • N-Methylscopolamine / antagonists & inhibitors
          • N-Methylscopolamine / pharmacokinetics
          • Pulmonary Disease, Chronic Obstructive / drug therapy
          • Pulmonary Disease, Chronic Obstructive / metabolism
          • Pulmonary Disease, Chronic Obstructive / veterinary
          • Receptors, Muscarinic / biosynthesis
          • Receptors, Muscarinic / drug effects
          • Receptors, Muscarinic / metabolism
          • Respiratory System / drug effects
          • Respiratory System / metabolism

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          Citations

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