Biomaterial Database

Influence of epithelium on the inhibition of melittin-induced contraction of guinea-pig isolated trachea by the potassium channel opener NIP-121. 1993

K Shikada, and S Tanaka

Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd., Saitama, Japan.

1. We have investigated the effect of the potassium channel opener, NIP-121, on contraction elicited by melittin (a phospholipase A2 activator) in epithelium-intact and epithelium-denuded trachea isolated from guinea-pigs. The effects of NIP-121 were compared with those of isoprenaline, aminophylline and hydrocortisone. 2. In the presence of the cyclo-oxygenase inhibitor, indomethacin (5 microM), melittin (3 micrograms ml-1) caused time-dependent contraction. The melittin-induced contractile response was significantly augmented by removal of the epithelium and was concentration-dependently and completely inhibited by the phospholipase A2 (PLA2) inhibitor, p-bromophenacyl bromide (BPB 10-100 microM), and the lipoxygenase inhibitor, phenidone (10-300 microM). Similar inhibition of the melittin response by BPB (10 microM) and phenidone (10 microM) was observed in the epithelium-denuded trachea. 3. Concentration-dependent inhibition of the melittin response was induced by preincubation with NIP-121 (0.03 and 0.1 microM), isoprenaline (0.001 and 0.01 microM), aminophylline (30 and 100 microM) and hydrocortisone (100 and 300 microM). The effect of NIP-121 was abolished by glibenclamide (1 microM). 4. The inhibitory effect of NIP-121 on the melittin response was greatly reduced by removing the epithelium while that of the isoprenaline, aminophylline or hydrocortisone was not changed. 5. The inhibition of the melittin response by these drugs was similar to their inhibition of the contraction elicited by a low concentration (3 nM) of leukotriene D4 (LTD4) in the epithelium-intact trachea. Inhibition of the LTD4 response by NIP-121 was not observed in the epithelium-denuded trachea. However, higher concentrations of NIP-121 (0.3 and 1 microM) did inhibit LTD4-induced contractions of epithelium-denuded trachea.6. These findings suggest that melittin causes epithelium-dependent contraction of the guinea-pig isolated trachea which is mediated by products of lipoxygenase activity. NIP-121 may inhibit the melittin response by activating glibenclamide-sensitive potassium channels, which appear to be epithelium-dependent (an indirect effect of NIP-121 apart from its direct effect on the airway smooth muscle) while isoprenaline, aminophylline and hydrocortisone act directly to relax the trachealis smooth muscle.

UI	MeSH Term	Description	Entries
D007545	Isoproterenol	Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.	Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D008297	Male		Males
D008555	Melitten	Basic polypeptide from the venom of the honey bee (Apis mellifera). It contains 26 amino acids, has cytolytic properties, causes contracture of muscle, releases histamine, and disrupts surface tension, probably due to lysis of cell and mitochondrial membranes.	Melittin,Mellitin
D009119	Muscle Contraction	A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.	Inotropism,Muscular Contraction,Contraction, Muscle,Contraction, Muscular,Contractions, Muscle,Contractions, Muscular,Inotropisms,Muscle Contractions,Muscular Contractions
D009130	Muscle, Smooth	Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)	Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D010069	Oxadiazoles	Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms.	Oxadiazole
D010880	Piperidines	A family of hexahydropyridines.
D004848	Epithelium	The layers of EPITHELIAL CELLS which cover the inner and outer surfaces of the cutaneous, mucus, and serous tissues and glands of the body.	Mesothelium,Epithelial Tissue,Mesothelial Tissue,Epithelial Tissues,Mesothelial Tissues,Tissue, Epithelial,Tissue, Mesothelial,Tissues, Epithelial,Tissues, Mesothelial
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006854	Hydrocortisone	The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.	Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol