Characterization of the in vitro responses of equine cecal longitudinal smooth muscle to endothelin-1.
Abstract: To characterize the in vitro response of equine cecal longitudinal smooth muscle (CLSM) to endothelin (ET)-1 and assess the role of ETA and ETB receptors in those ET-1-induced responses. Methods: 36 horses without gastrointestinal tract disease. Methods: To determine cumulative concentration-response relationships, CLSM strips were suspended in tissue baths containing graded concentrations of ET-1 (10(-9) to 10(-6)M) with or without BQ-123 (ETA receptor antagonist); with or without IRL-1038 (ETB receptor antagonist); or with both antagonists at concentrations of 10(-9), 10(-7), and 10(-5)M. To determine the percentage change in baseline tension of CLSM, the areas under the curve during the 3-minute periods before and after addition of each dose were compared. Also, the effects of ET-1 and a combination of selective ETA and ETB receptor antagonists on electrically evoked contractions were studied. Results: ET-1 caused sustained increases in CLSM tension in a concentration-dependent manner. Contractile responses to ET-1 were not significantly inhibited by either BQ-123 or IRL-1038 alone at any concentration; however, responses were significantly inhibited by exposure to the antagonists together at a concentration of 10(-5)M. Electrical field stimulation did not change the spontaneous contractile activity of CLSM and did not significantly alter the tissue response to ET-1, BQ-123, or IRL-1038. Conclusions: Results indicated that ET-1 has a contractile effect on equine CLSM that is mediated via ETA and ETB receptors. In vitro spontaneous contractions of equine CLSM apparently originate in the smooth muscle and not the enteric nervous system.
Publication Date: 2005-08-23 PubMed ID: 16111159DOI: 10.2460/ajvr.2005.66.1202Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article investigates how endothelin-1, a type of peptide, affects the contraction of smooth muscle in horse intestines in a lab setting and tries to understand how two types of receptors might influence this effect.
Research Methodology
- Thirty-six healthy horses were used in this study and a particular form of smooth muscle from their intestines, cecal longitudinal smooth muscle (CLSM), was isolated for investigation.
- To understand how ET-1 interacts with CLSM, muscle strips were submerged in varying concentrations of ET-1 ranging from 10(-9) to 10(-6)M.
- Some samples were also treated with either BQ-123 or IRL-1038, which are antagonists for ETA or ETB receptors, or both. The antagonists were used in three different concentrations, 10(-9), 10(-7), and 10(-5)M.
- By comparing the tension in the muscle before and after adding each dose, the researchers could determine how much ET-1 affected the smooth muscle’s contraction.
- CLSM contraction was also tested with the application of an electrical stimulus to understand if it would change its spontaneous activity or response to ET-1, BQ-123 or IRL-1038.
Research Findings
- The researchers found that ET-1 was able to increase the tension in the CLSM in a direct relationship to the concentration of ET-1; the higher the concentration of ET-1, the more sustained the increased tension in the muscle.
- The contractile responses to ET-1 were not noticeably affected when just one type of the antagonists (either BQ-123 for ETA receptors or IRL-1038 for ETB receptors) was present at any of the tested concentrations.
- In contrast, when both antagonists were used together at a concentration 10(-5)M, it significantly reduced the effects of ET-1 on the muscle strips’ contraction.
- Applying an electrical field to the muscle did not alter either its natural contraction or its response to ET-1, BQ-123, or IRL-1038, suggesting that its spontaneous contractions do not originate from the enteric nervous system.
Conclusions
- The study’s findings showed that ET-1 does have a contractile effect on horse’s intestinal smooth muscle (CLSM). This means it could potentially increase the motility or movement within the horse’s gastrointestinal tract.
- The researchers also concluded that this interaction involves both ETA and ETB receptors, as the antagonists for both of these receptors were able to inhibit the effects of ET-1 when used together.
- The enteric nervous system, which is part of the autonomic nervous system and helps regulate the function of the gastrointestinal tract, does not appear to be involved in the spontaneous contractions of CLSM, as electrical stimulation did not affect its behavior.
Cite This Article
APA
Chidambaram RM, Eades SC, Moore RM, Hosgood G, Venugopal CS.
(2005).
Characterization of the in vitro responses of equine cecal longitudinal smooth muscle to endothelin-1.
Am J Vet Res, 66(7), 1202-1208.
https://doi.org/10.2460/ajvr.2005.66.1202 Publication
Researcher Affiliations
- Equine Health Studies Program, Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410, USA.
MeSH Terms
- Animals
- Cecum / physiology
- Dose-Response Relationship, Drug
- Endothelin Receptor Antagonists
- Endothelin-1 / pharmacology
- Endothelin-1 / physiology
- Endothelins / pharmacology
- Horses / physiology
- In Vitro Techniques
- Muscle Contraction / drug effects
- Muscle Contraction / physiology
- Muscle, Smooth / physiology
- Peptide Fragments / pharmacology
- Peptides, Cyclic / pharmacology
Citations
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