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Updated: Aug 11, 2026
In vitro Measurements of Tracheal Constriction Using Mice
Published on: June 25, 2012
Agonist interactions at the calcium pools in skinned and unskinned canine tracheal smooth muscle
M S Kannan1, C Davis, A R Ladenius
1Department of Neurosciences, McMaster University Health Sciences Centre, Hamilton, Ont., Canada.
Abstract:
We studied the functionally discrete calcium sources used by acetylcholine, 5-hydroxytryptamine, histamine and high K+ in the dog tracheal smooth muscle. The extracellular calcium dependence of their responses was assessed by altering the calcium and by pretreatment with the calcium antagonist, nifedipine. The intracellular calcium pool was assessed by studying the interactions between caffeine and the agonists in both skinned and unskinned preparations. The extent of overlap for the different calcium pools between the various agonists was determined by studying the dose-response relationships of these agents before and after pretreatment with another agonist, i.e., the conditioning agonist, in zero calcium conditions. The rank order of sensitivity to calcium removal and to nifedipine was histamine greater than KCl greater than 5-hydroxytryptamine greater than acetylcholine. Caffeine-induced atenuation of the agonist responses was predominantly through physiological antagonism. However, the caffeine responses in unskinned fibres were augmented by pretreatment with the agonists through both nifedipine-sensitive (as with KCl) and -insensitive (as with acetylcholine) mechanisms. The responses to acetylcholine and caffeine were inhibited by theophylline and forskolin. In the skinned muscle fibres, the pCa-tension relationship suggested high calcium sensitivity, a significant caffeine-sensitive calcium pool, and no evidence of calcium release by exogenous inositol trisphosphate. The results are consistent with multiple extracellular and intracellular calcium sources for the agonist responses. We observed considerable overlap of the calcium sources used by these agonists. Of the four agonists studied, histamine appeared to inhibit the release and sequestration of calcium utilized by the other agonists most effectively.
Insights
This study reveals distinct calcium sources in dog tracheal smooth muscle for acetylcholine, histamine, and other agonists. Histamine most effectively modulated calcium release and uptake by other agents.
Area of Science:
- Pharmacology
- Smooth Muscle Physiology
- Calcium Signaling
Background:
- Acetylcholine, 5-hydroxytryptamine, histamine, and high K+ induce contractions in dog tracheal smooth muscle.
- Understanding the specific calcium sources utilized by these agonists is crucial for smooth muscle function.
Purpose of the Study:
- To investigate the distinct extracellular and intracellular calcium sources employed by acetylcholine, 5-hydroxytryptamine, histamine, and high K+ in dog tracheal smooth muscle.
- To determine the overlap and interactions between these calcium sources and the effects of various agonists.
Main Methods:
- Assessed extracellular calcium dependence by altering calcium concentrations and using the antagonist nifedipine.
- Investigated intracellular calcium pools via caffeine interactions in skinned and unskinned muscle preparations.
- Determined agonist calcium pool overlap by analyzing dose-response relationships before and after conditioning with other agonists in zero calcium.
Main Results:
- Rank order of sensitivity to calcium removal and nifedipine: histamine > KCl > 5-hydroxytryptamine > acetylcholine.
- Caffeine-induced attenuation of agonist responses was mainly physiological antagonism.
- Agonist pretreatment augmented caffeine responses via nifedipine-sensitive and insensitive mechanisms; acetylcholine and caffeine responses were inhibited by theophylline and forskolin.
- Skinned fibers showed high calcium sensitivity, a significant caffeine-sensitive pool, and no inositol trisphosphate-induced calcium release.
- Histamine most effectively inhibited calcium release/sequestration utilized by other agonists.
Conclusions:
- Dog tracheal smooth muscle utilizes multiple, overlapping extracellular and intracellular calcium sources for agonist-induced responses.
- Histamine plays a significant role in modulating the calcium dynamics of other agonists, impacting both release and sequestration processes.
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