SR 140333 prevents potentiation by citric acid of plasma exudation induced by histamine in airways.
We here report a model of potentiation by citric acid of airway microvascular leakage induced by histamine and its modification by the tachykinin NK1 and NK2 receptor antagonists, SR 140333 ((S)1-{2-[3-(3,4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)p iperidin- 3-yl]ethyl}-phenyl-1-azoniabicyclo[2.2.2]octane, chloride) and SR 48968 (S)-N-methyl-N-[4-(4-acetyl-amino-4-phenylpiperidino)-2-(3,4- dichlorophenyl-butyl]benzamide. Guinea-pigs exposed to an acrosol of citric acid 0.4 M for 1 h developed 24 h later a hyperresponsiveness to histamine-induced microvascular leakage measured by Evans blue dye extravasation. SR 140333, but not SR 48968 (1 mg kg-1 given each once 30 min before citric acid exposure), prevented this potentiation. These results provide further evidence of the role of tachykinin and tachykinin NK1 receptor stimulation on airway hyperresponsiveness and its neurogenic inflammatory component.
Biyah
K
K
Laboratoire de Pharmacologie, Faculté de Médecine Paris Ouest, France.
Molimard
M
M
Emonds-Alt
X
X
Advenier
C
C
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D019343:Citric Acid / Q000494:pharmacology*; D004357:Drug Synergism; D005122:Exudates and Transudates / Q000187:drug effects*; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D010949:Plasma / Q000502:physiology*; D011812:Quinuclidines / Q000494:pharmacology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D014132:Trachea / Q000187:drug effects* / Q000503:physiopathology
D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; C085215:SR 140333; D019343:Citric Acid; C073839:SR 48968; D006632:Histamine