Effect of AH5183 (vesamicol) on cholinergic transmission in intact airway smooth muscle.
The effect of the vesicular acetylcholine (ACh) transport blocker trans-2-(4- phenyl-piperidino)-cyclohexanol (AH5183) was studied in bronchial smooth muscle during activation of the vagus nerve. AH5183 inhibited in a dose-dependent manner the Ca(2+)-sensitive electrically induced smooth muscle contractions in vitro with a half-inhibitory concentration (IC50) of 1.6 +/- 0.4 microM. The inhibition was complete within 68 +/- 1 min (n = 8) at approximately 20 microM AH5183 and was partly reversible after washing of the preparations. AH5183 (20 microM) reduced the level of endogenous ACh by 47.4 +/- 7.6% (n = 4) during this time period. The effect of AH5183 is most likely prejunctional, since the contractions induced post-junctionally by carbachol were not altered by AH5183. The irreversible anticholinesterase, soman, increased the tonus of airway smooth muscle as a result of accumulation of spontaneously released ACh from prejunctional leakage. AH5183 had no effect on this increase of muscle contraction. The present results show that the nerve-evoked release of ACh comes from an AH5183-sensitive pool, probably a vesicular pool, whereas leakage of ACh presumably comes from the cytoplasmic pool in airway smooth muscle.
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Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller.
Gaudry-Talarmain
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Fonnum
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D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000201:enzymology / Q000294:innervation*; D002091:Butyrylcholinesterase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D009435:Synaptic Transmission / Q000187:drug effects*
D009467:Neuromuscular Depolarizing Agents; D010880:Piperidines; C006189:vesamicol; D002091:Butyrylcholinesterase; D000109:Acetylcholine