caa a22 4500 469078189 CHVBK 20180323132941.0 cr unu---uuuuu 170328e19920901xx s 000 0 eng 10.1007/BF00173551 doi (NATIONALLICENCE)springer-10.1007/BF00173551 Effect of calcium antagonists (ω-conotoxin GVIA, verapamil, gallopamil, diltiazem) on bronchial smooth muscle contractions induced by soman [Elektronische Daten] [Per Walday, Erik Fyllingen, Pål Aas] Summary: The effect of the calcium antagonists ω-conotoxin GVIA, verapamil, gallopamil and diltiazem was investigated on in vitro bronchial smooth muscle contraction in the rat induced by the nerve agent soman. Soman inhibits the acetylcholinesterase activity irreversibly. The effect of the calcium channel antagonists on contractions induced by electrical field stimulation and carbachol was also investigated, in order to elucidate the mechanism by which calcium antagonists inhibit the soman induced contraction. ω-Conotoxin GVIA reduced the bronchial smooth muscle contraction induced by electrical field stimulation with an almost complete inhibition at approximately 1.0× 10−6 M. The soman induced contraction was only inhibited by 15% at a concentration of 3.0× 10−6 M ω-conotoxin GVIA. The organic calcium antagonists verapamil, gallopamil and diltiazem reduced both electrically and soman induced smooth muscle contraction. Complete inhibition of the contractions induced by soman was achieved at 1.4x 10−4 M for verapamil and gallopamil, while diltiazem inhibited the contraction to 7% of control at 1.4 × 10−4 M. Verapamil, gallopamil and diltiazem increased the EC50 for carbachol significantly, while co-conotoxin GVIA had no effect. None of the calcium antagonists had any effect on the maximal contraction induced by carbachol. Verapamil, gallopamil and diltiazem blocked, however, sub-maximal contractions induced by carbachol (10−7 -10−5 M) resulting in a right-shift of the dose response curve. The results show that co-conotoxin GVIA inhibits the calcium-dependent release of acetylcholine which causes contraction of airway smooth muscle, while it has no effect on smooth muscle contraction induced by soman. Gallopamil, verapamil and diltiazem inhibit the contraction of bronchial smooth muscle following stimulation of postjunctional muscarinic receptors resulting from inhibition of the acetylcholinesterase activity by soman. Gallopamil and verapamil inhibit the contraction more potently than diltiazem. Springer-Verlag, 1992 Airway smooth muscle nationallicence Vagus nerve nationallicence Acetylcholine nationallicence Calcium antagonists nationallicence Walday Per Division for Environmental Toxicology, Norwegian Defence Research Establishment, N-2007, Kjeller, Norway aut Fyllingen Erik Division for Environmental Toxicology, Norwegian Defence Research Establishment, N-2007, Kjeller, Norway aut Aas Pål Division for Environmental Toxicology, Norwegian Defence Research Establishment, N-2007, Kjeller, Norway aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 352-357 0028-1298 346:3<352 1992 346 210 https://doi.org/10.1007/BF00173551 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00173551 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Walday Per Division for Environmental Toxicology, Norwegian Defence Research Establishment, N-2007, Kjeller, Norway aut NATIONALLICENCE 700 1- Fyllingen Erik Division for Environmental Toxicology, Norwegian Defence Research Establishment, N-2007, Kjeller, Norway aut NATIONALLICENCE 700 1- Aas Pål Division for Environmental Toxicology, Norwegian Defence Research Establishment, N-2007, Kjeller, Norway aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/3(1992-09-01), 352-357 0028-1298 346:3<352 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer