caa a22 4500 46907843X CHVBK 20180323132942.0 cr unu---uuuuu 170328e19921001xx s 000 0 eng 10.1007/BF00171091 doi (NATIONALLICENCE)springer-10.1007/BF00171091 The relaxant effects of cromakalim (BRL 34915) on human isolated airway smooth muscle [Elektronische Daten] [J. Cortijo, B. Sarriá, C. Pedrós, M. Perpiñá, F. Paris, E. Morcillo] Summary: Cromakalim (BRL 34915) is a potassium channel opener with therapeutic potential as a bronchodilator in asthma. Cromakalim (0.1-30 μmol/l) inhibited the spontaneous tone of human isolated bronchi n a concentration-related manner being nearly as effective as isoprenaline or theophylline. The order of relaxant potencies (expressed as -log10 IC50 mol/l; mean ±SEM) was isoprenaline (7.29 ± 0.27; n = 8) > cromakalim (5.89 ± 0.12; n = 7) > theophylline (4.07 ±0.13; n = 10). In human bronchi where tone had been raised by addition of histamine (0.1 mmol/l), acetylcholine (0.1 mmol/l) or leukotriene D4 (LTD4, 0.1 μmol/l), the relaxant effect of cromakalim was substantially reduced. Cromakalim suppressed the contraction produced by KCI (25 mmol/l) but not that produced by KCl (120 mmol/l). Tetraethylammonium (8 mmol/l) was without effect against the relaxant action of cromakalimbut procaine (0.5 - 5 mmol/l) and glibenclamide (0.3 μmol/l) antagonised it. Cromakalim (10 μmol/l) produced an upward displacement of concentration-effect curves forKCI (1-100 mmol/l), acetylcholine (1 nmol/l-1 mmol/) and histamine (1 nmol/l-1 mmol/l) but it did not alter the concentration-effect curve for LTD4 (0.1 nmol/l-0.1 μmol/l). When tissues were challenged in the presence of cromakalim (10 μmol/l) with KCI (100 mmol/l), acetylcholine (1 mmol/l) or histamine (1 mmol/l), an enhanced contraction was observed compared to control tissues. This enhancement by cromakalim was absent when tissues were challenged with acetylcholine or histamine in either a Ca2+-free medium (plus EGTA 0.1 mmol/l) or in the presence of verapamil (10 μmol/l). It is concluded that cromakalim is an effective relaxant of human airway smooth muscle in vitro and this activity may depend on the opening of K+ channels in the plasma membrane of smooth muscle cells but other actions cannot be ruled out. Springer-Verlag, 1992 Cromakalim nationallicence Human airway smooth muscle nationallicence Cortijo J. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut Sarriá B. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut Pedrós C. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut Perpiñá M. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut Paris F. Department of Thorácic Surgery, C. S. "La Fe”, Valencia, Spain aut Morcillo E. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/4(1992-10-01), 462-468 0028-1298 346:4<462 1992 346 210 https://doi.org/10.1007/BF00171091 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00171091 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cortijo J. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut NATIONALLICENCE 700 1- Sarriá B. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut NATIONALLICENCE 700 1- Pedrós C. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut NATIONALLICENCE 700 1- Perpiñá M. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut NATIONALLICENCE 700 1- Paris F. Department of Thorácic Surgery, C. S. "La Fe”, Valencia, Spain aut NATIONALLICENCE 700 1- Morcillo E. Department of Pharmacology, Faculty of Medicine, University of Valencia, Av. Blasco Ibañez 15, E-46010, Valencia, Spain aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/4(1992-10-01), 462-468 0028-1298 346:4<462 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer