Role of cAMP and neuronal K+ channels on alpha 2-AR-induced inhibition of ACh release in equine trachea.
Abstract: To investigate the effects of changes in intracellular cAMP on alpha 2-adrenoceptor (AR)-induced inhibition of airway acetylcholine (ACh) release, we examined the effects of the alpha 2-AR agonist clonidine on electrical field stimulation-evoked ACh release from equine tracheal parasympathetic nerves before and after treatment with 8-bromo-cAMP or forskolin. We also tested whether charybdotoxin (ChTX)- or iberiotoxin (IBTX)-sensitive Ca(2+)-activated K+ channels mediate alpha 2-AR-induced inhibition by examining the effect of clonidine in the absence and presence of ChTX or IBTX on ACh release. The amount of released ACh was measured by HPLC coupled with electrochemical detection. Clonidine (10(-7) to 10(-5) M) dose dependently inhibited ACh release before and after treatment with 8-bromo-cAMP (10(-3) M) or forskolin (3 x 10(-5) M). ChTX and IBTX, both at the concentration of 5 x 10(-7) M, significantly increased ACh release; however, they did not alter the magnitude of clonidine-induced inhibition. These results indicated that in equine tracheal parasympathetic nerves, alpha 2-AR-induced inhibition of ACh release is via an intracellular cAMP-independent pathway. Activation of both ChTX- and IBTX-sensitive Ca(2+)-activated K+ channels inhibits the electrical field stimulation-evoked ACh release, but these channels are not involved in the alpha 2-AR-induced inhibition of ACh release.
Publication Date: 1998-06-05 PubMed ID: 9612299DOI: 10.1152/ajplung.1998.274.5.L827Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article focuses on investigating the role of intracellular cAMP and specific potassium channels on the inhibition of acetylcholine (ACh) release in horse trachea due to alpha 2-adrenoceptors (AR). It concludes that alpha 2-AR reduces ACh release through a cAMP-independent pathway and while certain potassium channels can inhibit ACh release, they aren’t involved in alpha 2-AR induced inhibition.
Objective of the Study
- The key objective of this study was to explore how the changes in intracellular cAMP impact the alpha 2-adrenoceptor (AR)-induced restriction of acetylcholine (ACh) release in the equine trachea. Acetylcholine (ACh) is a significant neurotransmitter, and any modification in its release can influence several physiological processes.
Methods Employed
- Researchers examined the effects of the alpha 2-AR stimulating compound clonidine on induced ACh release from horse tracheal parasympathetic nerves, before and after the treatment with 8-bromo-cAMP or forskolin, compounds known to increase cAMP levels.
- Researchers studied whether Charybdotoxin (ChTX) or Iberiotoxin (IBTX)-sensitive Ca(2+)-activated potassium channels had a role in mediating alpha 2-AR-induced inhibition by studying the effect of clonidine in the absence and presence of these toxins on ACh release.
- ACh release was measured by High-Performance Liquid Chromatography (HPLC) coupled with electrochemical detection.
Result Analysis
- Clonidine was found to inhibit ACh release in a dose-dependent manner before and after treatment with compounds that increase cAMP levels.
- Both ChTX and IBTX significantly increased ACh release, however, they did not alter the degree of clonidine-induced inhibition.
Conclusions
- Researchers concluded that the alpha 2-AR-induced inhibition of ACh release operates via a pathway which is independent of intracellular cAMP levels in horse tracheal parasympathetic nerves. This means that alterations in cAMP within the cells do not influence the function of alpha 2-ARs in terms of inhibiting ACh release.
- They also found that activation of Ca(2+)-activated potassium channels sensitive to ChTX and IBTX does inhibit the release of ACh. However, these channels are not involved in the alpha 2-AR-induced inhibition of ACh release, meaning they function through a different mechanism. This illustrates the complexity of the systems regulating neurotransmitter release.
Cite This Article
APA
Zhang XY, Zhu FX, Robinson NE.
(1998).
Role of cAMP and neuronal K+ channels on alpha 2-AR-induced inhibition of ACh release in equine trachea.
Am J Physiol, 274(5), L827-L832.
https://doi.org/10.1152/ajplung.1998.274.5.L827 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, Michigan State University, East Lansing 48824-1314, USA.
MeSH Terms
- 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
- Acetylcholine / antagonists & inhibitors
- Acetylcholine / metabolism
- Adrenergic alpha-Agonists / pharmacology
- Animals
- Calcium / physiology
- Charybdotoxin / pharmacology
- Clonidine / pharmacology
- Colforsin / pharmacology
- Cyclic AMP / physiology
- Electric Stimulation
- Horses
- Neurons / metabolism
- Peptides / pharmacology
- Potassium Channel Blockers
- Potassium Channels / physiology
- Receptors, Adrenergic, alpha / physiology
- Trachea / metabolism
Citations
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