Contractile and phosphatidylinositol responses of rat trachea to anticholinesterase drugs

• Published in: Canadian journal of anesthesia 1998-12, Vol.45 (12), p.1190-1195
• Main Authors: SHIBATA, O, TSUDA, A, MAKITA, T, IWANAGA, S, HARA, T, SHIBATA, S, SUMIKAWA, K
• Format: Article
• Language: English
• Subjects: Anesthetics. Neuromuscular blocking agents; Animals; Biological and medical sciences; Carbachol - pharmacology; Cholinergic Agonists - pharmacology; Cholinesterase Inhibitors - pharmacology; Dimethylphenylpiperazinium Iodide - pharmacology; Edrophonium - pharmacology; Glucose; Inositol - metabolism; Inositol Phosphates - metabolism; Male; Medical sciences; Muscarinic Antagonists - pharmacology; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Muscular system; Neostigmine - pharmacology; Neuromuscular Blocking Agents - pharmacology; Neuropharmacology; Nicotinic Agonists - pharmacology; Organ Preservation Solutions; Pharmacology. Drug treatments; Phosphatidylinositols - metabolism; Piperidines - pharmacology; Proteins; Pyridostigmine Bromide - pharmacology; Radiopharmaceuticals; Rats; Rats, Wistar; Rodents; Smooth muscle; Tetrodotoxin - pharmacology; Trachea - drug effects; Tritium; Tromethamine
• ISSN: 0832-610X; 1496-8975
• DOI: 10.1007/bf03012462

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. Contractile response. Rat tracheal ring was suspended between two stainless hooks in Krebs-Henseleit (K-H) solution. (1) 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 neostigmine- or 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 and 3[H]myo-inositol in the presence of neostigmine or pyridostigmine with or without 4-DAMP, an M3 muscarinic receptor antagonist. 3[H]inositol monophosphate (IP1) formed was counted with a liquid scintillation counter. Carbachol (0.1 microM), neostigmine (1 microM), pyridostigmine (10 microM) but not edrophonium or DMPP, caused tracheal ring contraction. 4-DAMP, but not tetrodotoxin, inhibited neostigmine and pyridostigmine-induced contraction. Neostigmine- or pyridostigmine-induced IP1, accumulation was inhibited by 4-DAMP. The data suggest that anti-ChE drugs activate the M3 receptors at the tracheal effector site.