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Differential calcium movements induced by agonists in guinea pig tracheal muscle
Abstract:
The effects of high potassium, carbachol and histamine on tension responses and 45Ca fluxes in tracheal smooth muscle were examined. Calcium depletion or nitrendipine (10(-8) M) inhibited potassium-induced contractile responses more than those obtained with either histamine or carbachol, whereas Sr2+ inhibited mainly responses to histamine or carbachol. The Ca2+ entry facilitator, CGP 28392 (3 X 10(-6) M), potentiated contractions induced only by potassium. Uptake of 45Ca in guinea pig tracheal muscle can be separated into high and low affinity components. The 45Ca efflux rate from tracheal muscle into a La3+-substituted solution was over four-fold higher than in other smooth muscles. Potassium, carbachol and histamine induced sustained increases in 45Ca efflux into solutions containing 1.5 mM Ca2+; only transient increases in 45Ca efflux with carbachol and histamine were obtained after Ca2+ depletion. These agonists elicit contractile responses in tracheal muscle by selectively mobilizing different cellular and extracellular Ca2+ components.
Insights
High potassium, carbachol, and histamine affect tracheal smooth muscle tension and calcium (Ca2+) movement differently. These agonists activate distinct cellular and extracellular calcium sources for muscle contraction.
Area of Science:
- Pharmacology
- Physiology
- Cell Biology
Background:
- Tracheal smooth muscle contraction is regulated by calcium (Ca2+) influx and release.
- Understanding the specific Ca2+ pathways activated by different agonists is crucial for respiratory medicine.
Purpose of the Study:
- To investigate how high potassium, carbachol, and histamine influence tension and Ca2+ fluxes in guinea pig tracheal smooth muscle.
- To differentiate the roles of extracellular and intracellular Ca2+ sources in agonist-induced contractions.
Main Methods:
- Measurement of isometric tension responses in isolated guinea pig trachealis.
- Quantification of 45Ca uptake and efflux under various conditions, including Ca2+ depletion and in the presence of specific inhibitors (nitrendipine) or facilitators (CGP 28392).
- Use of strontium (Sr2+) as a Ca2+ substitute to probe specific pathways.
Main Results:
- Potassium-induced contractions were more sensitive to Ca2+ depletion and nitrendipine than histamine or carbachol responses.
- Sr2+ primarily affected histamine and carbachol responses, suggesting different Ca2+ handling mechanisms.
- The Ca2+ facilitator CGP 28392 specifically potentiated potassium-induced contractions.
- Agonists induced sustained 45Ca efflux, with carbachol and histamine showing transient efflux after Ca2+ depletion, indicating mobilization of both extracellular and intracellular Ca2+ pools.
Conclusions:
- Potassium, carbachol, and histamine activate distinct Ca2+ mobilization pathways in tracheal smooth muscle.
- Agonist-induced contractile responses are mediated by the selective recruitment of different cellular and extracellular Ca2+ components.
- These findings provide insights into the differential regulation of airway smooth muscle tone.