Involvement of tachykinin NK1 receptors in plasma protein extravasation induced by tachykinins in the guinea pig upper airways.
Plasma protein extravasation in the upper airways of anesthetized guinea pigs was measured with the FITC (Fluorescein isothiocyanate)-dextran technique. The effect of selective tachykinin (NK1 and NK2) receptor agonists and antagonists, capsaicin or antigen was studied. The tachykinin NK1 receptor agonist, [Sar9]substance P sulfone, induced an increase in FITC-dextran extravasation which was blocked by the nasal application (30-100 nmol/kg) of the tachykinin NK1 receptor antagonist FK888, but not by 1 micromol/kg of the tachykinin NK2 receptor antagonist, MEN10,627. The tachykinin NK2 receptor agonist, [betaAla8]neurokinin A-(4-10), had no effect on dye leakage. FK888 (30 nmol/kg intranasal) abolished the increase in the tracer recovery induced both by antigen and capsaicin. Conversely, the intranasal administration of MEN10,627 (0.1-1.0 micromol/kg) significantly reduced capsaicin-induced and only marginally inhibited antigen-induced increase in plasma protein extravasation. Pretreatment with the neutral endopeptidase inhibitor, phosphoramidon, increased the effect of all inflammatory agents. These findings show that the plasma extravasation of the upper airways induced by exogenous or endogenous tachykinins is primarily mediated by tachykinin NK1 receptors. This inflammatory response could be controlled by locally applied tachykinin NK1 receptor antagonist.
Evangelista
S
S
Department of Pharmacology, Istituto Farmacobiologico Malesci S.p.A., Firenze, Italy.
Paoli
S
S
Giachetti
A
A
Manzini
S
S
D000818:Animals; D000941:Antigens / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D003911:Dextrans / Q000493:pharmacokinetics; D004151:Dipeptides / Q000494:pharmacology; D005119:Extravasation of Diagnostic and Therapeutic Materials; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009297:Nasal Mucosa / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D018034:Olfactory Receptor Neurons / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000819:agonists / Q000378:metabolism*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D012220:Rhinitis / Q000276:immunology / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology
D000941:Antigens; D001798:Blood Proteins; D003911:Dextrans; D004151:Dipeptides; D006020:Glycopeptides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C015219:fluorescein isothiocyanate dextran; C062618:substance P, Sar(9)-Met(O2)(11)-; C064218:neurokinin A (4-10), beta-Ala(8)-; C078949:FK 888; C090951:MEN 10627; D013373:Substance P; D015288:Neurokinin A; D016650:Fluorescein-5-isothiocyanate; D002211:Capsaicin; C008890:phosphoramidon