Effect of the K+ channel openers NIP-121 and cromakalim on melittin-induced relaxation of guinea-pig isolated trachea
| Autor: | Ken-ichi Shikada, Sakuya Tanaka |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
Cromakalim Contraction (grammar) Potassium Channels Stereochemistry Muscle Relaxation Guinea Pigs Indomethacin complex mixtures Biochemistry Melittin Epithelium Phospholipases A Leukotriene D4 chemistry.chemical_compound Thromboxane A2 Endocrinology Phospholipase A2 Piperidines Animals Channel blocker Benzopyrans Cyclooxygenase Inhibitors Drug Interactions Pyrroles Oxadiazoles biology Dose-Response Relationship Drug Muscle Smooth respiratory system Melitten Prostaglandin Endoperoxides Synthetic Enzyme Activation Trachea Phospholipases A2 chemistry 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid biology.protein Biophysics lipids (amino acids peptides and proteins) Cyclooxygenase Histamine |
| Zdroj: | Prostaglandins. 51(5) |
| ISSN: | 0090-6980 |
| Popis: | We have investigated the effect of the K+ channel openers (+)-7,8-dihydro-6, 6-dimethyl-7-hydroxy-8-(2-oxo-piperidin-1-yl)-6H-pyrano[2,3- f]benz-2, 1,3-oxadiazole (NIP-121) and cromakalim on the relaxation induced by the phospholipase A2 activator melittin in guinea-pig isolated trachea. Melittin (0.1 to 3.0 micrograms/ml) caused concentration-dependent relaxation of tracheal spirals precontracted with LTD4. The magnitude of relaxation was about 40% of that obtained by 1 mM aminophylline. Melittin-induced relaxation was also observed in tracheas precontracted with histamine or the thromboxane A2 mimetic U46619. The relaxation to melittin was prevented by the cyclooxygenase inhibitor indomethacin (5 microM) or by removal of the tracheal epithelium, suggesting that cyclooxygenase products, possibly dependent on the epithelium, may be implicated in the response to melittin. Pretreatment of tracheas with NIP-121 (0.03 microM) or cromakalim (0.4 microM) did not affect the contraction to LTD4 but enhanced the relaxation to melittin. This enhancement to melittin was completely inhibited by the ATP-dependent K+ channel blocker glibenclamide (1 microM). Higher concentrations of NIP-121 (0.1 microM) or cromakalim (1 microM) did not enhance the response to melittin. In the presence of indomethacin, NIP-121 (0.03 microM) or cromakalim (0.4 microM) enhanced PGE2-induced relaxation of tracheas precontracted with LTD4. These results suggest that cyclooxygenase products, possibly dependent on the epithelium, may be involved in melittin-induced relaxation. The enhancement of relaxation to melittin by K+ channel activation might be due, at least in part, to an increased inhibitory response to cyclooxygenase products [corrected]. |
| Databáze: | OpenAIRE |
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