Relative potencies of 5-lipoxygenase inhibitors on antigeninduced contractions of guinea pig tracheal strips
| Autor: | David W. Snyder, Peter P.K. Ho, Edward David Mihelich, Hwei Ling Cho |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Male
Ovalbumin medicine.drug_class Guinea Pigs Tetrazoles In Vitro Techniques Pharmacology Guinea pig medicine Animals Potency Lipoxygenase Inhibitors Antigens Receptors Immunologic Receptor Receptors Leukotriene Leukotriene biology Acetophenones Receptor antagonist Trachea Mechanism of action Biochemistry Enzyme inhibitor Arachidonate 5-lipoxygenase biology.protein Biological Assay medicine.symptom Muscle Contraction |
| Zdroj: | Journal of Pharmacological Methods. 26:277-287 |
| ISSN: | 0160-5402 |
| Popis: | A quantitative method to assess relative potencies (IC 50 ) of 5-lipoxygenase (5-LO) enzyme inhibitors was established in antigen-induced contractions of tracheas isolated from actively sensitized guinea pigs (Schultz-Dale model). The relative potencies of four purported 5-LO inhibitors determined in this tissue assay were compared with those from a crude enzyme preparation isolated from guinea pig neutrophils. All compounds suppressed ovalbumin (OA)-induced tracheal contractions in a concentration-related manner in the presence of indomethacin and pyrilamine. IC 50 Values, determined from the percent inhibition values obtained from responses at 30 ng/mL OA of these compounds ranged from 0.56–15 μM. A similar rank order of potency for inhibition of 5-HETE formation from a crude enzyme preparation was observed. This suggested that these agents had a common mechanism of action in the two assay systems and further validated the IC 50 values determined in trachea assay. LY171883, an LTD 4 /LTE 4 receptor antagonist, also suppressed OA-induced contractions concentration dependently with an IC 50 of 4.9 μM determined by this method. LTD 4 concentration-response curves were not altered by any of the four 5-LO inhibitors, ruling out the possibility that these agents were acting as LT receptor antagonists. Results of this study demonstrated that relative potencies of 5-LO inhibitors can be quantitatively assessed using this airway tissue model, which helps in identifying potential therapeutic agents for asthma. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|