title: Tachykinin NK(3) receptor agonists induced microvascular leakage hypersensitivity in the guinea-pig airways.
abstract: Microvascular leakage hypersensitivity is a main component of neurogenic inflammation and of tachykinin effects. The aim of this study was to examine the ability of neurokinin B and of the tachykinin NK(3) receptor agonists, [MePhe(7)]neurokinin B or senktide, to potentiate when given by aerosol the microvascular leakage induced by histamine in guinea-pig airways and to compare their effects to those of tachykinin NK(1) (substance P, [Sar(9),Met(O(2))(11)]substance P) or tachykinin NK(2) (neurokinin A, [betaAla(8)]neurokinin A (4-10)) receptor agonists. Guinea-pigs were pretreated successively for 10 min with aerolized salbutamol and phosphoramidon; 15 min later, they were exposed for 30 min to an aerosolized solution of tachykinin receptor agonists; 24 h later, the animals were anaesthetized and vascular permeability was quantified by extravasation of Evans blue dye. Neurokinin B, [MePhe(7)]neurokinin B and senktide (3 x 10(-6)-3 x 10(-5)M) induced a potentiation of the effects of histamine on the vascular permeability in the trachea and main bronchi. Compared to other tachykinin NK(1) and NK(2) receptor agonists, the order of potency was: senktide>neurokinin B=[Sar(9),Met(O(2))(11)]substance P=[betaAla(8)]neurokinin A (4-10)=[MePhe(7)]neurokinin B>neurokinin A>substance P. The potentiation by [MePhe(7)]neurokinin B of histamine-induced microvascular leakage was abolished by the tachykinin NK(1) receptor antagonist SR140333 ([(S)1-(2-[3-(3,4-dichlorophenyl)-1-(3-iso-propoxyphenylacetyl)piperidin-3-yl]etyl)-4-phenyl-1-azoniabicyclo[2.2.2]octane, chloride]) or the tachykinin NK(3) receptor antagonists SR 142801 ([(R)-(N)-(1-(3-(l-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl) propyl)-4-phenylpiperidin-4-yl)-N-methylacetamide]) and SB 223412 ([(S)-(-)-N-(alpha-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carboxamide]). In conclusion, these results suggest that tachykinin NK(3) receptors might be involved in the potentiation of histamine-induced increase in microvascular permeability.
authors.affiliation: UFR Biomédicale des Saints-Pères, Faculté de Médecine Paris-Ouest, UPRES EA220-Pharmacologie, 45 Rue des Saints Pères, F-75006 Paris, France.
authors.forename: S
authors.initials: S
authors.lastname: Daoui
authors.forename: A
authors.initials: A
authors.lastname: Ahnaou
authors.forename: E
authors.initials: E
authors.lastname: Naline
authors.forename: X
authors.initials: X
authors.lastname: Emonds-Alt
authors.forename: V
authors.initials: V
authors.lastname: Lagente
authors.forename: C
authors.initials: C
authors.lastname: Advenier
mesh_terms: D000336:Aerosols; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000209:etiology; D002199:Capillary Permeability / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008297:Male; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D018042:Receptors, Neurokinin-3 / Q000819:agonists* / Q000502:physiology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000336:Aerosols; D018042:Receptors, Neurokinin-3; C080394:neurokinin B, MePhe(7)-; D006632:Histamine; D015287:Neurokinin B