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Potentiation of acetylcholine release from tracheal parasympathetic nerves by cAMP.
Abstract: We tested the hypothesis that increasing intracellular levels of adenosine 3', 5'-cyclic monophosphate (cAMP) increases acetylcholine (ACh) release from airway parasympathetic nerves. Muscle strips from equine trachea were preincubated for 60 min with 10(-7)M atropine, 10(-6)M neostigmine, and 10(-5) M guanethidine. The ACh release was evoked by electrical field stimulation (EFS, 20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography with electrochemical detection. Agents known to increase cAMP, i.e., forskolin (10(-6) - 10(-4) M), 8-bromoadenosine 3', 5'-cyclic monophosphate (8-BrcAMP; 10(-5)-10(-3) M), and 3-isobutyl-1-methylxanthine (IBMX ; 10(-5)-10(-3)M) was potentiated by IBMX but not mimicked by 1,9 dideoxyforskolin. To determine if the augmentation of Ach release facilitated EFS-induced ACh release in a concentration-dependent manner. Forskolin-induced augmentation of ACh release induced by activation of beta 2-adrenoceptors is mediated via cAMP-dependent pathways, we also examined the additive effects of 8-BrcAMP, forskolin, and IBMX with 10(-6)M isoproterenol (ISO), the concentration that maximally augments ACh release. Neither forskolin nor 8-BrcAMP potentiated the maximal augmentation produced by ISO, but inhibition of phosphodiesterase with IBMX (10(-4) and 10(-3)M) augmented the maximal effect of ISO. These observations indicate that neuronal cAMP is a physiological modulator of ACh release from airway parasympathetic nerves and mediates ISO-induced augmentation of ACh release. Bronchodilators that increase cAMP may therefore paradoxically augment ACh release while relaxing smooth muscle.
Publication Date: 1996-04-01 PubMed ID: 8928813DOI: 10.1152/ajplung.1996.270.4.L541Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- U.S. Gov't
- P.H.S.
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research conducted experiments to establish that increasing levels of a molecule called cAMP (adenosine 3′, 5′-cyclic monophosphate) effectively enhances the release of acetylcholine from nerves in the airway. They found that cAMP serves as a physiological modulator and is responsible for acetylcholine release, which implies a potential impact on bronchodilators that are used to relax smooth muscle.
Experimental Procedure
- The study initiated its experiments with muscle strips from the trachea of horses. These strips were pre-soaked for an hour in a solution containing specific chemical compounds – Atropine, Neostigmine, and Guanethidine.
- To trigger the release of Acetylcholine (ACh), a neurotransmitter, they used an electrical field stimulation (EFS) approach.
- The ACh release was quantified using high-performance liquid chromatography combined with electrochemical detection.
- During the experiment, the researchers employed several agents known to boost the levels of cAMP, including forskolin, 8-BrcAMP, and IBMX.
Key Observations
- The researchers found that increasing the concentration level of cAMP indeed promoted the release of ACh from airway parasympathetic nerves.
- However, in their experiments, they noticed that forskolin’s increase did not potentiate the maximal augmentation that was achieved by using isoproterenol (ISO), a β2 adrenergic agonist.
- Conversely, when they inhibited Phosphodiesterase with IBMX, they noticed a significant enhancement of the ISO’s maximal effect.
Conclusions of the Study
- The study concluded that neuronal cAMP can be considered a physiological modulator of ACh release from airway parasympathetic nerves.
- This implies that bronchodilators, which are generally used to relax smooth muscles in conditions like asthma, could inadvertently enhance the ACh release if they increase cAMP.
- This paradoxical reaction could potentially have important implications for how bronchodilators are formulated and used in medical treatments.
Cite This Article
APA
Zhang XY, Robinson NE, Zhu FX.
(1996).
Potentiation of acetylcholine release from tracheal parasympathetic nerves by cAMP.
Am J Physiol, 270(4 Pt 1), L541-L546.
https://doi.org/10.1152/ajplung.1996.270.4.L541 Publication
Researcher Affiliations
- Department of Large Animal Clinical Science, Michigan State University, East Lansing 48824, USA.
MeSH Terms
- 1-Methyl-3-isobutylxanthine / pharmacology
- 8-Bromo Cyclic Adenosine Monophosphate / pharmacology
- Acetylcholine / metabolism
- Animals
- Colforsin / pharmacology
- Cyclic AMP / physiology
- Electric Stimulation
- Horses
- In Vitro Techniques
- Isoproterenol / pharmacology
- Parasympathetic Nervous System / metabolism
- Trachea / innervation
Grant Funding
- HL-49494 / NHLBI NIH HHS
Citations
This article has been cited 1 times.- Pauwelyn V, Lefebvre RA. cAMP Catalyzing Phosphodiesterases Control Cholinergic Muscular Activity But Their Inhibition Does Not Enhance 5-HT(4) Receptor-Mediated Facilitation of Cholinergic Contractions in the Murine Gastrointestinal Tract. Front Pharmacol 2018;9:171.
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