In vivo evidence for the activation of a septide-sensitive tachykinin receptor in guinea pig bronchoconstriction.
Intravenous administration of the undecapeptide [Sar9]substance P (SP) sulfone (1.5 nmol/kg) and the hexapeptide [Glp6,Pro9]SP(6-11) (septide; 0.4 nmol/kg) produced a comparable (about 30-40% of maximal effect) increase of insufflation pressure (bronchospasm) in anesthetized guinea-pigs. The non peptide NK-1 receptor antagonist, (+/-)CP 96,345 and the peptide NK-1 receptor antagonist, GR 82,334 antagonized dose-dependently the response to both agonists. Both antagonists were more potent against septide than against [Sar9]SP sulfone (9 and 4 fold difference in ED50 for (+/-)CP 96,345 and GR 82,334, respectively). These findings indicate that a 'septide-sensitive' mechanism mediates bronchoconstriction in vivo and it influences the estimate of the potency of NK-1 receptor antagonists.
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Pharmacology Department, Malesci Pharm., Firenze, Italy.
Maggi
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Evangelista
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D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001986:Bronchial Spasm / Q000139:chemically induced / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010803:Physalaemin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology*
D001713:Biphenyl Compounds; D006993:Hypnotics and Sedatives; D010446:Peptide Fragments; D018039:Receptors, Tachykinin; D013450:Sulfones; C062618:substance P, Sar(9)-Met(O2)(11)-; C079014:GR 82334; D010803:Physalaemin; D013373:Substance P; C054725:septide; D011761:Pyrrolidonecarboxylic Acid; C066892:CP 96345