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Protein kinase C and tracheal contraction at low temperature
C K Huang1, M Munakata, J M Baraban
1Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland.
The Journal of Pharmacology and Experimental Therapeutics
|October 1, 1987
Summary
Temperature significantly impacts airway tone regulation. Cooling activates the lipoxygenase pathway via Protein Kinase C (PKC) activation, potentially altering airway responses during conditions like exercise-induced asthma.
Area of Science:
- Physiology
- Biochemistry
- Pharmacology
Background:
- Airway cooling occurs during exercise or dry air exposure.
- The role of temperature in regulating airway tone is not fully understood.
- Protein Kinase C (PKC) is a key mediator of cellular responses.
Purpose of the Study:
- To investigate if temperature changes affect PKC pathways in airways.
- To examine the influence of temperature on airway smooth muscle tone.
- To explore the mechanisms underlying temperature-dependent PKC signaling.
Main Methods:
- Used guinea pig tracheal rings.
- Applied phorbol esters (e.g., Phorbol-12,13-diacetate) to activate PKC.
- Tested responses at different temperatures (37°C and 22°C).
- Utilized ouabain or KCl to depolarize cell membranes.
- Administered lipoxygenase inhibitors and a leukotriene receptor antagonist.
Main Results:
- Phorbol-12,13-diacetate reduced tracheal tone at 37°C but increased it at 22°C.
- At 22°C, PDA-induced contractions were inhibited by lipoxygenase inhibitors and a leukotriene antagonist.
- PDA-induced contractions at 37°C, or at 22°C with depolarization, were unaffected by these inhibitors.
- Cooling shifts PKC-mediated responses towards the lipoxygenase pathway.
Conclusions:
- Temperature profoundly influences PKC-activated airway responses.
- Low temperatures engage the lipoxygenase pathway in PKC signaling.
- Airway cooling can modify intracellular pathways regulating physiological responses.