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Contractile and phosphatidylinositol responses of rat trachea to anticholinesterase drugs

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Abstract

Purpose

Some anticholinesterases (anti-ChE) such as neostigmine and pyridostigmine but not edrophonium, stimulate phosphatidylinositol (PI) response. Although a direct relationship was suggested between the increase in PI response and airway smooth muscle contraction, there are no data regarding the effects of anti-ChE drugs on airway smooth muscle. Thus, we examined the contractile properties and PI responses produced by anti-ChE drugs.

Methods

Contractile response. Rat tracheal ring was suspended between two stainless hooks in Krebs-Henseleit (K-H) solution. (I) Carbachol (CCh), anti-ChE drugs (neostigmine, pyridostigmine, edrophonium) or DMPP (a selective ganglionic nicotinic agonist) were added to induce active contraction. (2) The effects of 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), an M3 muscarinic receptor antagonist, on neostigmineor pyridostigmine-induced contraction of rat tracheal ring were examined. (3) Tetrodotoxin (TTX) was tested on the anti-ChE drugs-induced responses.PI response. The tracheal slices were incubated in K-H solution containing LiCl and3[H]myo-inositol in the presence of neostigmine or pyridostigmine with or without 4-DAMP, an M3 muscarinic receptor antagonist.3[H]inositol monophosphate (IP,) formed was counted with a liquid scintillation counter.

Results

Carbachol (0.1 μM), neostigmine (1 μM), pyridostigmine (10 μM) but not edrophonium or DMPP, caused tracheal ring contraction. 4-DAMP, but not tetrodotoxin, inhibited neostigmine and pyridostigmineinduced contraction. Neostigmineor pyridostigmine-induced IP1 accumulation was inhibited by 4-DAMP.

Conclusions

The data suggest that anti-ChE drugs activate the M3 receptors at the tracheal effector site.

Résumé

Objectif

Certains anticholinestérasiques (anti-ChE) comme la néostigmime et la pyridostigmine, mais non l’edrophonium, stimulent la réponse du phosphatidylinositol (PI). Bien qu’on ait évoqué une relation directe entre l’augmentation de la réponse PI et la contraction des muscles lisses du conduit aérien, il n’y a pas de données concernant les effets de médicaments anti-ChE sur les muscles lisses des voies aériennes. Donc, nous avons étudié les propriétés contractiles et les réponses du PI produites par les médicaments anti-ChE.

Méthode

Réponse contractile. Des anneaux de trachée de rat ont été suspendus entre des crochets inox dans une solution de Krebs-Henseleit (K-H). (1) Du carbachol (CCh), des médicaments anti-ChE (néostigmine, pyridostigmine, edrophonium) ou DMPP (un agoniste nicotinique ganglionnaire sélectif) ont été ajoutés pour induire une contraction active. (2) Les effets du méthobromide 4-diphénylacétoxy-N-méthyl-pipéridine (4-DAMP), un antagoniste des récepteurs muscariniques M3, sur la contraction d’anneaux de trachée de rat induite par la néostigmine ou la pyridostigmine, ont été examinés. (3) La tétrodotoxine (TTX) a été évaluée lors des réponses induites par les médicaments anti-ChE.Réponse PI. Les tranches de trachée ont été mises en incubation dans la solution K-H contenant du LiCI et3[H]myo-inositol en présence de néostigmine ou de pyridostigmine, avec ou sans 4-DAMP, un antagoniste des récepteurs muscariniques M3. Le monophosphate3[H]inositol (IP1) ainsi formé a été mesuré à l’aide d’un compteur à scintillation liquide.

Résultats

Le carbachol (0,1 μM), la néostigmine (1 μM), la pyridostigmine (10 μM) mais non l’edrophonium ou le DMPP ont causé des contraction des anneaux de trachée. La 4-DAMP contrairement à la tétrodotoxine, a inhibé les contractions induites par la néostigmine et la pyridostigmine. Laccumulation d’IP1 induite par la néostigmine ou la pyridostigmine a été inhibée par la 4-DAMP.

Conclusion

Les données indiquent que les médicaments anti-ChE activent les récepteurs M3 au site effecteur de la trachée.

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Correspondence to Osamu Shibata.

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Shibata, O., Tsuda, A., Makita, T. et al. Contractile and phosphatidylinositol responses of rat trachea to anticholinesterase drugs. Can J Anaesth 45, 1190 (1998). https://doi.org/10.1007/BF03012462

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Keywords

  • Muscarinic Receptor
  • Carbachol
  • Airway Smooth Muscle
  • Neostigmine
  • Pyridostigmine