Effect of glucocorticoid on upregulation of histamine H1 receptor mRNA in nasal mucosa of rats sensitized by exposure to toluene diisocyanate.
OBJECTIVE
Histamine is a major chemical mediator in the development of nasal allergy, which is characterized by nasal hypersensitivity. In this study, we used rats sensitized by exposure to toluene diisocyanate (TDI) as an animal model of nasal hypersensitivity and examined changes in expression of histamine H1 receptor (H1R) in the nasal mucosa. The effect of glucocorticoid on upregulation of H1R in nasal mucosa induced by TDI was also examined.


METHODS
In rats sensitized by exposure to TDI, nasal allergy-like behavior was scored during a 10-min period after TDI provocation. The expression of H1R in the nasal mucosa was determined by means of a real-time quantitative reverse transcriptase polymerase chain reaction and a [3H]mepyramine binding assay.


RESULTS
In TDI-sensitized rats, nasal allergy-like behavior, such as sneezing and watery rhinorrhea, was induced after intranasal application of TDI and nasal hypersensitivity to histamine was significantly increased. The level of H1R mRNA expression and the specific binding of [3H]mepyramine in the nasal mucosa were significantly increased after intranasal application of TDI in TDI-sensitized rats. Pretreatment with dexamethasone significantly reduced both nasal allergy-like behavior and the upregulation of H1R induced by TDI in the rats.


CONCLUSIONS
As shown in TDI-sensitized rats, our findings suggest that the upregulation of H1R in the nasal mucosa is one of the mechanisms responsible for nasal hypersensitivity behavior and nasal hypersensitivity to histamine and that the therapeutic effects of dexamethasone are, in part, due to its inhibitory action on the upregulation of H1R.
Kitamura
Yoshiaki
Y
Department of Otolaryngology, University of Tokushima School of Medicine, Tokushima, Japan. kitamura@clin.med.tokushima-u.ac.jp
Miyoshi
Ayako
A
Murata
Yuki
Y
Kalubi
Bukasa
B
Fukui
Hiroyuki
H
Takeda
Noriaki
N
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000276:immunology; D011897:Random Allocation; D051381:Rats; D011969:Receptors, Histamine H1 / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014051:Toluene 2,4-Diisocyanate; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; D011969:Receptors, Histamine H1; D014051:Toluene 2,4-Diisocyanate; D003907:Dexamethasone