The effect of indomethacin on the contractile response of the guinea-pig lung parenchymal strip to leukotrienes B4, C4, D4 and E4. 1983

K F Austen, and E J Corey, and J M Drazen, and A G Leitch

Indomethacin (1 microgram ml-1) almost totally inhibited the dose-dependent contractile response of isolated lung parenchymal strips of the guinea-pig (GPLS) to leukotriene B4 (LTB4) over the concentration range 0.18-18 nM. LTC4 (0.63 pM-63 nM)-induced contractions of GPLS were not significantly inhibited by indomethacin (1.0 and 10.0 micrograms ml-1) except when the highest LTC4 concentration (63 nM) was tested in the presence of indomethacin (10 micrograms ml-1). LTD4 (1.3 fM-13 nM)-induced contractions of GPLS were not significantly inhibited by indomethacin (0.1-10 micrograms ml-1) except for contractions induced by concentrations of LTD4 greater than 0.13 nM and 13 nM. Indomethacin 1 microgram ml-1 and 10 micrograms ml-1 inhibited the contractile response to 13 nM LTD4 by 37 and 16% respectively. LTE4 (2.3 fM-23 nM)-induced contractions of GPLS were not significantly inhibited by indomethacin (0.1-10 micrograms ml-1). Contraction due to LTE4 23 pM was significantly potentiated by indomethacin (1 microgram ml-1). Clotrimazole (10 microM) significantly inhibited LTD4-induced contractions of GPLS at concentrations greater than 13 pM but had no significant effect on LTC4-induced contractions. Cyclo-oxygenase products, probably principally thromboxane A2, are important secondary mediators of LTB4-induced contractions of GPLS but make little or no contribution to contractions of GPLS induced by LTC4, LTD4, and LTE4, except at higher concentrations of LTD4 and possibly LTC4. Certain concentrations of LTE4 may generate bronchodilator PGE2 in GPLS.

UI MeSH Term Description Entries
D007213 Indomethacin A non-steroidal anti-inflammatory agent (NSAID) that inhibits CYCLOOXYGENASE, which is necessary for the formation of PROSTAGLANDINS and other AUTACOIDS. It also inhibits the motility of POLYMORPHONUCLEAR LEUKOCYTES. Amuno,Indocid,Indocin,Indomet 140,Indometacin,Indomethacin Hydrochloride,Metindol,Osmosin
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
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
D003022 Clotrimazole An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal CELL MEMBRANES. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. Bay b 5097,Canesten,FB b 5097,Kanesten,Klotrimazole,Lotrimin,Mycelex
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
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
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013189 SRS-A A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed) Slow Reacting Substance of Anaphylaxis
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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