Mechanism of capsaicin-induced relaxation in equine tracheal smooth muscle.
Abstract: The effects of capsaicin and neuropeptides were examined in equine tracheal smooth muscle (TSM). Neither capsaicin nor substance P (SP) contracted TSM. Capsaicin (100 microM) elicited relaxation in TSM contracted with methacholine. This relaxation was not mimicked by SP or calcitonin gene-related peptide (CGRP). Relaxation was not attenuated by removal of the epithelium or by pretreatment of tissue with meclofenamate or the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine. Previous exposure of TSM to capsaicin did not eliminate the relaxation responses to subsequent capsaicin. Although vasoactive intestinal peptide (VIP) elicited marked relaxation that was attenuated by alpha-chymotrypsin, alpha-chymotrypsin did not affect the capsaicin-induced relaxation. Capsaicin-induced relaxation was abolished by charybdotoxin, a blocker of large-conductance Ca(2+)-activated K+ channels. These results indicate that capsaicin-induced equine TSM relaxation is not mediated either by neuropeptides such as SP or CGRP released from capsaicin-sensitive sensory nerves or by prostanoids, NO, or VIP. Relaxation is due to the effect of capsaicin on large-conductance Ca(2+)-activated K+ channels. The peptidergic nerves play no important role in the regulation of TSM tone in horse airways.
Publication Date: 1997-12-31 PubMed ID: 9374726DOI: 10.1152/ajplung.1997.273.5.L997Google Scholar: Lookup
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- Journal Article
Summary
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This research looks at the relaxing effect of capsaicin on equine tracheal smooth muscle (TSM), with findings suggesting that this relaxation isn’t influenced by neuropeptides, but is due to capsaicin’s impact on large-conductance calcium-activated potassium channels.
Objective and Approach
- The study set out to investigate the effect of capsaicin and specific neuropeptides on the tracheal smooth muscle (TSM) in horses.
- This included studying the effect of the removal of the epithelium, pretreating the tissue with meclofenamate and the nitric oxide synthase inhibitor NG-nitro-L-arginine on capsaicin-induced relaxation of TSM.
- Researchers both observed the responses of TSM to capsaicin over time and compared the relaxation effects of various substances, including capsaicin and vasoactive intestinal peptide (VIP).
Findings
- The researchers observed that neither capsaicin nor substance P (SP) caused the TSM to contract.
- However, they found that capsaicin significantly relaxed TSM that had been contracted with methacholine, a result not replicated by either SP or calcitonin gene-related peptide (CGRP).
- They also noted that past exposure of TSM to capsaicin did not prevent it from responding with relaxation to capsaicin in the future.
- Removal of the epithelium or pretreatment of tissue with specific substances did not lessen the relaxation effect that capsaicin had on TSM.
- Interestingly, while VIP elicited a marked relaxation effect that was weakened by alpha-chymotrypsin, the capsaicin-induced relaxation was not affected by alpha-chymotrypsin but was completely eliminated by charybdotoxin, a blocker of large-conductance Ca(2+)-activated K+ channels.
Conclusion
- The study concluded that capsaicin’s relaxing effect on equine TSM is not mediated by neuropeptides such as SP or CGRP released from capsaicin-sensitive sensory nerves or by prostanoids, NO, or VIP.
- Instead, the relaxation is due to capsaicin’s impact on large-conductance calcium-activated potassium channels.
- The research also indicates that peptidergic nerves do not play a significant role in the regulation of TSM tone in horse airways.
Cite This Article
APA
Zhu FX, Zhang XY, Olszewski MA, Robinson NE.
(1997).
Mechanism of capsaicin-induced relaxation in equine tracheal smooth muscle.
Am J Physiol, 273(5), L997-L1001.
https://doi.org/10.1152/ajplung.1997.273.5.L997 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Michigan State University, East Lansing 48824-1314, USA.
MeSH Terms
- Animals
- Calcitonin Gene-Related Peptide / pharmacology
- Capsaicin / pharmacology
- Charybdotoxin / pharmacology
- Chymotrypsin / pharmacology
- Epithelial Cells / physiology
- Horses
- In Vitro Techniques
- Large-Conductance Calcium-Activated Potassium Channels
- Methacholine Chloride / pharmacology
- Muscle Contraction / drug effects
- Muscle Relaxation / drug effects
- Muscle Relaxation / physiology
- Muscle, Smooth / drug effects
- Muscle, Smooth / innervation
- Muscle, Smooth / physiology
- Neurons, Afferent / drug effects
- Neurons, Afferent / physiology
- Neuropeptides / pharmacology
- Nitric Oxide / physiology
- Nitroarginine / pharmacology
- Potassium Channel Blockers
- Potassium Channels, Calcium-Activated
- Substance P / pharmacology
- Trachea / drug effects
- Trachea / innervation
- Trachea / physiology
- Vasoactive Intestinal Peptide / pharmacology
Citations
This article has been cited 4 times.- Van Crombruggen K, Van Nassauw L, Derycke L, Timmermans JP, Holtappels G, Hall D, Bachert C. Capsaicin-induced vasodilatation in human nasal vasculature is mediated by modulation of cyclooxygenase-2 activity and abrogated by sulprostone. Naunyn Schmiedebergs Arch Pharmacol 2011 Jun;383(6):613-26.
- Venugopal CS, Holmes EP, Polikepahad S, Laborde S, Kearney M, Moore RM. Neurokinin receptors in recurrent airway obstruction: a comparative study of affected and unaffected horses. Can J Vet Res 2009 Jan;73(1):25-33.
- Gupta S, Lozano-Cuenca J, Villalón CM, de Vries R, Garrelds IM, Avezaat CJ, van Kats JP, Saxena PR, MaassenVanDenBrink A. Pharmacological characterisation of capsaicin-induced relaxations in human and porcine isolated arteries. Naunyn Schmiedebergs Arch Pharmacol 2007 Mar;375(1):29-38.
- Takahashi K, Toyohira Y, Ueno S, Tsutsui M, Yanagihara N. Capsaicin inhibits catecholamine secretion and synthesis by blocking Na+ and Ca2+ influx through a vanilloid receptor-independent pathway in bovine adrenal medullary cells. Naunyn Schmiedebergs Arch Pharmacol 2006 Nov;374(2):107-16.
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