Piperaquine To further clarify the vascular cell types expre
To further clarify the vascular cell types expressing AR subtypes, double immunofluorescence staining for ARs and vascular endothelial Piperaquine or vascular smooth muscles was performed. As shown in Fig. 3, Fig. 4, overlay images show the expression of all ARs subtypes that we examined in vascular endothelial cells. Similarly, overlay images show the expression of all ARs subtypes that we examined in vascular smooth muscles (Fig. 5, Fig. 6).
The patterns of other immunohistochemical findings in all 12 cases were remarkably similar, and no differences in AR immunoreactivity were observed between allergic and non-allergic nasal mucosa. The summary of these results is shown in Table 2.
Discussion The present immunohistochemical results suggested that nasal AR subtypes could be classified roughly into two types (blood vessel dominant type: α1A- and α2C-AR, and glandular dominant type: α1D- and β2-AR). In 2007, Stafford-Smith et al. demonstrated the localization of α-AR mRNA subtypes in the mucosa of human turbinates using in situ hybridization . In their study, the expression pattern of α1D-AR was mRNA is similar to that in our current immunohistochemical results. However, the expression patterns of α1A- and α2C-AR were different from those in our results. While Stafford-Smith et al. showed that all α-AR mRNA subtypes were localized in submucosal glands , we could not detect α2C-AR protein in submucosal glands. Additionally, our results showed that α1A-AR protein was localized primary in vascular smooth muscles; however, there was no evidence of α1A-AR mRNA expression in vessels in their previous report . Tanimitsu et al. suggested that activation of α1A-AR results in contraction of nasal vasculature in guinea pigs , supporting our present results. With regard to the roles of nasal α2C-AR, the topical administration of a selective α2C-AR agonist in experimental animal models of nasal congestion has shown that these agents have a significant role in basal nasal patency , . Moreover, these previous observations and our present results indicate that both α1A-AR and α2C-AR were localized nasal capacitance vessels, suggesting that activation of these AR subtypes lead to be venous constriction of the collecting veins and sinusoids. While vasoconstriction is thought to be a major effect of topical α-AR agonists, other targets are also possible because of α-AR protein expression in epithelial cells and submucosal glands. Topical administration of phenylpropanolamine, an agonist of α1- and α2-ARs, significantly reduces histamine-induced nasal secretion in healthy subjects . Conversely, α1-AR antagonists, which are standard medications for benign prostatic hyperplasia (BPH), may cause sever rhinorrhea . Thus, activation of glandular α-AR may lead to inhibition of nasal glandular secretion. Our present immunohistochemical studies clearly showed the expression of β2-AR protein in nasal submucosal glands. With regards to the expression of nasal β2-AR, a previous study showed that β2-AR mRNA is expressed in submucosal glands as demonstrated using in situ hybridization . Although the β2-AR agonist albuterol had no effect on glandular secretion from human nasal mucosa in vivo and in vitro , albuterol causes glandular secretion from dexamethasone-pretreated human nasal mucosa in vitro , suggesting that upregulation of β2-AR expression is required for β2-AR agonist-induced nasal glandular secretion. On the other hand, studies have also suggested that intranasal β2-AR agonists may be effective in the treatment of allergic rhinitis. In a double-blind investigation in patients with hay fever, nasal administration of the β2-AR agonist fenoterol was shown to have marked inhibitory effects on nasal allergen provocation-induced major nasal symptoms in doses ordinarily used for inhalation in the treatment of bronchial asthma . In addition, a placebo-controlled study showed that administration of the oral β2-AR agonist salbutamol significantly reduces nasal symptoms of seasonal rhinitis, with potential capacity to reduce the use of antihistamines in the salbutamol-treated group . Additionally, a single dose of the intranasal β2-AR agonist salmeterol was shown to reduce the allergen-induced increase in nasal lavage fluid albumin, suggesting effects on vascular permeability . From these observations, upregulation of β2-AR function by agonists or glucocorticoids may have beneficial effects in the treatment of allergic rhinitis.