Interactions of edrophonium with neostigmine in the rat trachea
| Autor: | Koji Sumikawa, Masakazu Yamaguchi, Tetsuji Makita, Masataka Saito, Maki Yoshimura, Osamu Shibata |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Allosteric regulation Edrophonium Pharmacology In Vitro Techniques Phosphatidylinositols Edrophonium Chloride chemistry.chemical_compound Muscarinic acetylcholine receptor medicine Animals Inosine Triphosphate Drug Interactions Phosphatidylinositol Rats Wistar Receptor Muscarinic M3 biology business.industry Muscarinic acetylcholine receptor M3 Muscle Smooth Receptors Muscarinic Neostigmine Rats Trachea Anesthesiology and Pain Medicine Biochemistry chemistry Parasympathomimetics Enzyme inhibitor biology.protein business medicine.drug Muscle Contraction |
| Zdroj: | Anesthesia and analgesia. 97(4) |
| ISSN: | 0003-2999 |
| Popis: | UNLABELLED The muscarinic M(3) receptor of airway smooth muscle has both an orthosteric binding site and an allosteric binding site. Edrophonium may bind to the allosteric site, resulting in the inhibition of the action of the orthosteric site. Therefore, we examined the effects of edrophonium on neostigmine-induced contractile and phosphatidylinositol responses of rat trachea. Neostigmine (100 micro M in final concentration) was added, and ring tension was examined by the addition of edrophonium. After the completion of the experiment, Krebs-Henseleit (K-H) solution containing both edrophonium and neostigmine was changed three times with fresh K-H solution, and the tension was recorded. Tracheal slices were incubated with [(3)H]myo-inositol and 100 micro M neostigmine in the presence or absence of edrophonium. The [(3)H]inositol monophosphate (IP(1)) was measured. Data were expressed as mean +/- SE. Statistical significance (P < 0.05) was determined with analysis of variance. Neostigmine-induced tension and IP(1) accumulation were attenuated by edrophonium at concentrations of 100 micro M or more. This attenuation was reversed to more than 80% of control levels by washing with fresh K-H solution. The results suggest that edrophonium would bind to the allosteric site, resulting in the inhibition of the action of the orthosteric site of muscarinic M(3) receptors of rat trachea. IMPLICATIONS We examined the effects of edrophonium on neostigmine-induced contractile and phosphatidylinositol responses of rat trachea. Neostigmine-induced tension and inositol monophosphate accumulation were attenuated by edrophonium. This attenuation was reversed by washing. The results suggest that edrophonium would bind to the allosteric site. |
| Databáze: | OpenAIRE |
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