Effects of the peptide leukotriene receptor antagonist ICI 198,615 on the in vivo and in vitro changes in guinea pig bladder function which occur after sensitization with ovalbumin. 1995

J G Lee, and R M Levin, and L Krasnopolsky, and A J Wein, and P A Longhurst
Division of Urology, University of Pennsylvania School of Medicine, Philadelphia, USA.

OBJECTIVE The present studies were designed to determine the effects of in vivo and in vitro administration of ICI 198,615 (ICI), a leukotriene receptor antagonist, on the inflammatory changes that occur in the bladder after sensitization with ovalbumin. METHODS The effect of intravenous administration of ICI on urodynamic changes after instillation of ovalbumin to sensitized guinea pigs was evaluated by in vivo cystometry. Responses of in vitro bladder muscle strips to contractile stimuli and ovalbumin were also evaluated in the presence of ICI. RESULTS In sensitized guinea pigs, in vivo cystometry with ovalbumin induced a marked decrease in bladder capacity and increase in intravesical pressure. Pretreatment with ICI prior to cystometry prevented the ovalbumin-induced changes in capacity and intravesical pressure. There were no significant differences between control and sensitized animals in the responses of in vitro bladder muscle strips to field stimulation or bethanechol. However, maximal contractile responses to ovalbumin were significantly greater in the strips from sensitized animals than in controls. Preincubation with ICI, indomethacin, or pyrilamine alone was unable to inhibit the contractile responses to ovalbumin. However, combined administration of ICI, indomethacin and pyrilamine completely blocked the responses. CONCLUSIONS In vivo administration of the leukotriene receptor antagonist ICI 198,615 reversed the urodynamic changes induced by ovalbumin challenge in sensitized guinea pigs. These results indicate that leukotrienes are primarily responsible for the changes in in vivo bladder function associated with sensitization.

UI MeSH Term Description Entries
D007191 Indazoles A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES. Indazole
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
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
D010047 Ovalbumin An albumin obtained from the white of eggs. It is a member of the serpin superfamily. Serpin B14
D011738 Pyrilamine A histamine H1 antagonist. It has mild hypnotic properties and some local anesthetic action and is used for allergies (including skin eruptions) both parenterally and locally. It is a common ingredient of cold remedies. Mepyramine,Pyranisamine,Anthisan,Boots Bite & Sting Relief,Kriptin,Mepyramine Maleate,Pyrilamine Maleate,Maleate, Mepyramine,Maleate, Pyrilamine
D001743 Urinary Bladder A musculomembranous sac along the URINARY TRACT. URINE flows from the KIDNEYS into the bladder via the ureters (URETER), and is held there until URINATION. Bladder,Bladder Detrusor Muscle,Detrusor Urinae,Bladder Detrusor Muscles,Bladder, Urinary,Detrusor Muscle, Bladder,Detrusor Muscles, Bladder
D005260 Female Females
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

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