neurokinin-a and Rhinitis

Topics: Bradykinin; Calcitonin Gene-Related Peptide; Cytokines; Eicosanoids; Histamine H1 Antagonists; Humans; Nasal Mucosa; Nasal Polyps; Neurokinin A; Neuropeptide Y; Platelet Activating Factor; Receptors, Calcitonin Gene-Related Peptide; Rhinitis; Substance P; Vasoactive Intestinal Peptide

The purposes of the present study were i) to determine whether neuropeptides induce the nasal obstruction in guinea pigs, and ii) to examine the possible involvement of neuropeptides in allergic nasal obstruction. The decrease in nasal cavity volume was determined by acoustic rhinometry as an index of nasal obstruction. In non-sensitized guinea pigs, substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) caused the nasal obstruction 10 to 30 min after their intranasal application. LY303870 (1 mg/kg), a tachykinin NK1-receptor antagonist; SR48968 (1 mg/kg), a tackykinin NK2-receptor antagonist; and CGRP(8-37) (50 nmol/kg), a CGRP1-receptor antagonist, administered intravenously before the intranasal application of the neuropeptides, inhibited the responses induced by SP, NKA and CGRP, respectively. In the guinea pigs sensitized with dinitrophenyl-coupled Ascaris suum allergenic extract, the intranasal antigen challenge caused nasal obstruction. The response was biphasic and consisted of the early phase response (EPR) and the late phase response (LPR), which developed 30 min and 6 h, respectively, after the antigen challenge. Intravenous administration of LY303870 (1 mg/kg) before the antigen challenge inhibited the EPR, while those of SR48968 (1 mg/kg) and CGRP(8-37) (50 nmol/kg) inhibited the LPR. The present results suggest that neuropeptides are involved in the allergic nasal obstruction.

Topics: Animals; Calcitonin Gene-Related Peptide; Guinea Pigs; Hypersensitivity; Male; Miotics; Nasal Cavity; Nasal Obstruction; Neurokinin A; Neuropeptides; Peptide Fragments; Rhinitis; Substance P

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.

Topics: Animals; Antigens; Blood Proteins; Capsaicin; Dextrans; Dipeptides; Extravasation of Diagnostic and Therapeutic Materials; Fluorescein-5-isothiocyanate; Glycopeptides; Guinea Pigs; Indoles; Male; Nasal Mucosa; Neurokinin A; Neurokinin-1 Receptor Antagonists; Olfactory Receptor Neurons; Peptide Fragments; Peptides, Cyclic; Protease Inhibitors; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Rhinitis; Substance P