Contractile and phosphatidylinositol responses of rat trachea to anticholinesterase drugs.
OBJECTIVE
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. (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.


RESULTS
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.


CONCLUSIONS
The data suggest that anti-ChE drugs activate the M3 receptors at the tracheal effector site.
Shibata
O
O
Department of Anesthesiology, Nagasaki University School of Medicine, Japan.
Tsuda
A
A
Makita
T
T
Iwanaga
S
S
Hara
T
T
Shibata
S
S
Sumikawa
K
K
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004491:Edrophonium / Q000494:pharmacology; D005947:Glucose; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009388:Neostigmine / Q000494:pharmacology; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D019188:Organ Preservation Solutions; D010716:Phosphatidylinositols / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects*; D014316:Tritium; D014325:Tromethamine
D018679:Cholinergic Agonists; D002800:Cholinesterase Inhibitors; D007295:Inositol Phosphates; C074097:Krebs-Henseleit solution; D018727:Muscarinic Antagonists; D009466:Neuromuscular Blocking Agents; D018722:Nicotinic Agonists; D019188:Organ Preservation Solutions; D010716:Phosphatidylinositols; D010880:Piperidines; D019275:Radiopharmaceuticals; D014325:Tromethamine; D014316:Tritium; D009388:Neostigmine; D013779:Tetrodotoxin; D007294:Inositol; D004246:Dimethylphenylpiperazinium Iodide; D004491:Edrophonium; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D002217:Carbachol; D005947:Glucose; D011729:Pyridostigmine Bromide