In vitro functional interactions of acetylcholine esterase inhibitors and muscarinic receptor antagonists in the urinary bladder of the rat
Language English Country Australia Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- Keywords
- acetylcholinesterase inhibition, heart, muscarinic M2 receptor, rat, urinary bladder,
- MeSH
- Muscarinic Antagonists pharmacology MeSH
- Atropine pharmacology MeSH
- Cholinesterase Inhibitors pharmacology MeSH
- Diamines pharmacology MeSH
- Physostigmine pharmacology MeSH
- Receptor Cross-Talk MeSH
- Rats MeSH
- Methacholine Chloride pharmacology MeSH
- Urinary Bladder drug effects enzymology metabolism MeSH
- Obidoxime Chloride pharmacology MeSH
- Receptor, Muscarinic M2 antagonists & inhibitors MeSH
- Receptor, Muscarinic M3 antagonists & inhibitors MeSH
- Heart Atria drug effects enzymology metabolism MeSH
- Muscle Contraction drug effects MeSH
- In Vitro Techniques MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Muscarinic Antagonists MeSH
- Atropine MeSH
- Cholinesterase Inhibitors MeSH
- Diamines MeSH
- Physostigmine MeSH
- Methacholine Chloride MeSH
- methoctramine MeSH Browser
- Obidoxime Chloride MeSH
- Receptor, Muscarinic M2 MeSH
- Receptor, Muscarinic M3 MeSH
Obidoxime, a weak acetylcholine-esterase (AChE) inhibitor, exerts muscarinic receptor antagonism with a significant muscarinic M2 receptor selective profile. The current examinations aimed to determine the functional significance of muscarinic M2 receptors in the state of AChE inhibition, elucidating muscarinic M2 and M3 receptor interaction. In the in vitro examinations, methacholine evoked concentration-dependent bladder contractile and atrial frequency inhibitory responses. Although atropine abolished both, methoctramine (1 μmol/L) only affected the cholinergic response in the atrial preparations. However, in the presence of methoctramine, physostigmine, an AChE inhibitor, increased the basal tension of the bladder strip preparations (+68%), as well as the contractile responses to low concentrations of methacholine (< 5 μmol/L; +90-290%). In contrast to physostigmine, obidoxime alone raised the basal tension (+58%) and the responses to low concentrations of methacholine (< 5 μmol/L; +80-450%). Physostigmine concentration-dependently increased methacholine-evoked responses, similarly to obidoxime at low concentrations. However, at large concentrations (> 5 μmol/L), obidoxime, because of its unselective muscarinic receptor antagonism, inhibited the methacholine bladder responses. In conclusion, the current results show that muscarinic M2 receptors inhibit muscarinic M3 receptor-evoked contractile responses to low concentrations of acetylcholine in the synaptic cleft. The muscarinic M2 and M3 receptor crosstalk could be a counteracting mechanism in the treatment of AChE inhibition when using reactivators, such as obidoxime.
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