The effect of acetylcholinesterase-inhibition on the tonus of guinea-pig bronchial smooth muscle.
The irreversible acetylcholinesterase inhibitor soman (O-[1,2,2-trimethylpropyl]-methyl-phosphonofluoridate) induced contraction of guinea-pig primary bronchial smooth muscle. The apparent affinity (ED50) of acetylcholine (ACh) was altered from control value of 12 microM to 0.3 microM following exposure of the bronchial smooth muscle to 14 microM soman for 15 min in vitro. The ED50 of the cholinergic agonist carbachol was not changed even when the acetylcholinesterase (AChE) activity was inhibited completely. The intrinsic activity (alpha) of ACh and carbachol was not significantly changed after exposure to soman for 15 min. The results demonstrate that the effect of soman is only due to its anticholinesterase activity. Furthermore, the contraction induced by histamine was not altered by concentrations of soman which increase the cholinergic stimulation. This indicates that histamine does not induce contraction of bronchial smooth muscle in guinea pig through the release of ACh or by modulation of muscarinic receptors. Furthermore, soman also inhibited the carboxylesterase activity in the primary bronchi. In respiratory tissue this group of enzymes may have a major protective function, due to their ability to bind several organophosphorus compounds. Compared to studies performed on other species, this study shows that guinea-pig bronchi are very sensitive to the AChE-inhibitor soman. Therefore, exposure to very low concentrations of AChE-inhibitors may induce contraction of bronchial smooth muscle.
Aas
P
P
Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller.
Walday
P
P
Tansø
R
R
Fonnum
F
F
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D002091:Butyrylcholinesterase / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D004558:Electric Stimulation; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D012999:Soman / Q000494:pharmacology*
D006632:Histamine; D002217:Carbachol; D012999:Soman; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase