Involvement of neuropeptides in the allergic nasal obstruction in guinea pigs.
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.
Kaise
T
T
Department of Pharmacology, Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., Sunto-gun, Shizuoka, Japan. toshihiko.kaise@kyowa.co.jp
Akamatsu
Y
Y
Ikemura
T
T
Ohmori
K
K
Ishii
A
A
Karasawa
A
A
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000009:adverse effects; D006168:Guinea Pigs; D006967:Hypersensitivity / Q000209:etiology*; D008297:Male; D008916:Miotics / Q000009:adverse effects; D009296:Nasal Cavity / Q000187:drug effects / Q000276:immunology; D015508:Nasal Obstruction / Q000139:chemically induced / Q000276:immunology; D015288:Neurokinin A / Q000009:adverse effects; D009479:Neuropeptides / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000009:adverse effects; D012220:Rhinitis / Q000139:chemically induced / Q000276:immunology; D013373:Substance P / Q000009:adverse effects
D008916:Miotics; D009479:Neuropeptides; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D013373:Substance P; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide