Differential antagonism of airway contractile responses to prostaglandin (PG)D2 and 9 alpha, 11 beta-PGF2 by atropine, SKF 88046 and SQ 29,548 in the guinea pig
| Autor: | D C, Underwood, R M, Muccitelli, M A, Luttmann, D W, Hay, T J, Torphy, M A, Wasserman |
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| Rok vydání: | 1994 |
| Předmět: |
Atropine
Male Sulfonamides Prostaglandin D2 Guinea Pigs Receptors Prostaglandin Receptors Thromboxane In Vitro Techniques Bridged Bicyclo Compounds Heterocyclic Dinoprost Acetylcholine Receptors Thromboxane A2 Prostaglandin H2 Bronchoconstrictor Agents Trachea Thromboxane A2 Hydrazines Fatty Acids Unsaturated Animals Muscle Contraction |
| Zdroj: | The Journal of pharmacology and experimental therapeutics. 268(1) |
| ISSN: | 0022-3565 |
| Popis: | PGD2, the predominant prostanoid released from activated human lung mast cells, is metabolized to 9 alpha, 11 beta-PGF2 by an 11-ketoreductase. Both prostanoids contract mammalian airway smooth muscle. In the present study, aerosol administration of PGD2 or 9 alpha, 11 beta-PGF2 (five puffs of 10-50 micrograms/ml) to anesthetized, spontaneously breathing guinea pigs produced significant increases in airway resistance and decreases in dynamic lung compliance. The changes in airway resistance and dynamic lung compliance induced by 50 micrograms/ml were reduced approximately 60% and 25%, respectively, by pretreatment with atropine (1 mg/kg, i.v., -10 min). Pretreatment with the TxA2 receptor antagonist SKF 88046 (N,N'-bis[7-(3-chlorobenzene aminosulfonyl)-1,2,3,4- tetrahydroisoquinolyl]disulfonylimide) (5 mg/kg, i.v., -10 min), nearly abolished the changes in airway resistance and dynamic lung compliance that were elicited by both agonists. Pretreatment with a TxA2 synthase inhibitor, CGS 13080 (10 mg/kg, i.v., -10 min), had no effect on PGD2- or 9 alpha, 11 beta-PGF2-induced bronchoconstriction, suggesting that these prostanoids did not provoke the release of TxA2. In vitro, PGD2, 9 alpha, 11 beta-PGF2 and a TxA2 mimic, U-44069, produced concentration-dependent contractions of the guinea pig isolated trachea with pD2s of 6.4, 6.0 and 7.2, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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