Antagonism of peptidoleukotrienes and inhibition of systemic anaphylaxis by RG 12525 in guinea pigs
RG 12525 was determined to be a specific, competitive and orally effective antagonist of the peptidoleukotrienes, LTC/sub 4/, LTD/sub 4/ and LTE/sub 4/, in several assays utilizing guinea pigs. In vitro, RG 12525 competitively inhibited /sup 3/H-LTD/sub 4/ binding to lung membranes and competitively antagonized the spasmogenic activity of LTC/sub 4/, LTD/sub 4/ and LTE/sub 4/ on lung strips with > 8000 fold selectivity. In vivo, RG 12525 orally inhibited LTD/sub 4/ induced wheal formation LTD/sub 4/ induced bronchoconstriction and anaphylactic death and antigen induced bronchoconstriction. RG 12525 represents a significant improvement in receptor affinity and oral efficacy and thus, is a valuable pharmacological tool to evaluate peptidoleukotrienes in allergic diseases.
- Research Organization:
- Rorer Central Research, Horsham, PA (USA)
- OSTI ID:
- 6149918
- Journal Information:
- Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 44:13; ISSN LIFSA
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
BRONCHI
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
DISEASES
DRUGS
GUINEA PIGS
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LUNGS
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
ORAL ADMINISTRATION
ORGANIC COMPOUNDS
ORGANS
PATHOGENESIS
PROTEINS
REACTION KINETICS
RECEPTORS
RESPIRATORY SYSTEM
RESPIRATORY SYSTEM DISEASES
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOCONSTRICTION
VASOCONSTRICTORS
VASODILATORS
VERTEBRATES