Histamine H1 receptor and reactivity of the nasal mucosa in sensitized guinea pigs.
OBJECTIVE
Nasal Hypersensitivity to histamine is higher in allergic patients than that in normal control, suggesting that affinity and/or density of H1 receptors in nasal mucosa may be increased in patients with allergic rhinitis. The purpose in this study is to examine the correlation between the hyperresponsiveness and number of histamine H1 receptors in guinea pig nasal mucosa.


METHODS
Guinea pigs were sensitized by DNP-Ascaris antigen. To block histamine H1 receptors, ketotifen was used and the number of receptors was counted by receptor binding assay technique. These data were compared with nasal airway volume (VOL) assessed by acoustic rhinometry of the same animals to know whether the number of H1 receptors is correlated to the nasal responsiveness to the antigen, or not. Eighty animals were divided into five groups which are composed of nonsensitized and sensitized group pretreated with saline, 0.1, 1.0 and 10 mg/kg of ketotifen, respectively.


RESULTS
The number of H1 receptors (Bmax) was significantly increased in sensitized group compared with that in control. It decreased dose dependently by pretreatment of ketotifen. The percent change of VOL showed - 31.1 +/- 4.1% at 10 min and - 42.9 +/- 4.1% at 30 min after antigen challenge in sensitized animals. This was dose dependently inhibited by ketotifen. There was a highly inverse correlation between VOL and Bmax (r = -0.708, P< 0.0001).


CONCLUSIONS
These results suggest that sensitization increases the number of histamine H1 receptor, and that increased number of H1 receptor in nasal mucosa in sensitized guinea pigs may be one of the causes of nasal hyperresponsiveness to antigen.
Ohkawa
C
C
Department of Otorhinolaryngology, Mie University School of Medicine, Tsu, Japan.
Ukai
K
K
Miyahara
Y
Y
Takeuchi
K
K
Sakakura
Y
Y
D000284:Administration, Oral; D000818:Animals; D001200:Ascaris / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology*; D015508:Nasal Obstruction / Q000276:immunology; D009299:Nasal Provocation Tests; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology*
D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D007665:Ketotifen