Alpha-adrenergic mRNA subtype expression in the human nasal turbinate

Abstract

Purpose: Alpha-adrenergic receptor (AR) agonist drugs (e.g., epinephrine) are commonly used for upper airway procedures, to shrink the mucosa, retard absorption of local anesthetic agents, and improve visualization by limiting hemorrhage. Decongestant therapy often also includes αAR agonist agents, however overuse of these drugs (e.g., oxymetazoline) can result in chronic rhinitis and rebound increases in nasal secretion. Since current decongestants stimulate αARs non-selectively, characterization of αAR subtype distribution in human airway (nasal turbinate) offers an opportunity to refine therapeutic targets while minimizing side-effects. We, therefore, investigated αAR subtype expression in human nasal turbinate within epithelial, duct, gland, and vessel cells using in situ hybridization. Methods: Since sensitive and specific anti-receptor antibodies and highly selective αAR subtype ligands are currently unavailable, in situ hybridization was performed on sections of three human nasal turbinate samples to identify distribution of αAR subtype mRNA. Subtype specific 35S-labelled mRNA probes were incubated with nasal turbinate sections, and protected fragments remaining after RNase treatment analyzed by light and darkfield microscopy. Results: In non-vascular tissue α1d AR mRNA predominates, whereas notably the α2c is the only αAR subtype present in the sinusoids and arteriovenous anastamoses. Conclusion: Combined with the current understanding that AR-mediated constriction of nasal sinusoids underpins decongestant therapies that minimize secretions and shrink tissues for airway procedures, these findings suggest that α2c AR subtypes provide a novel selective target for decongestant therapy in humans.