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,
* From the Departments of Anesthesiology,
Pharmacology/Cancer Biology, & Medicine (Pulmonary and Cardiology), and
Surgery, Duke University Medical Center, Durham, North Carolina; and the
Departments of Medicine and Pediatrics, Georgetown University, Washington, DC, USA.
Address correspondence to: Dr. Mark Stafford-Smith, Department of Anesthesiology, Duke University Medical Center, Box 3094, DUMC, Durham, NC 27710, USA. Phone: 919-681-5046; Fax: 919-681-8993 ; E-mail: staff002{at}mc.duke.edu
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
AR 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
ARs non-selectively, characterization of
AR subtype distribution in human airway (nasal turbinate) offers an opportunity to refine therapeutic targets while minimizing side-effects. We, therefore, investigated
AR 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
AR subtype ligands are currently unavailable, in situ hybridization was performed on sections of three human nasal turbinate samples to identify distribution of
AR 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
1d AR mRNA predominates, whereas notably the
2c is the only
AR 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
2c AR subtypes provide a novel selective target for decongestant therapy in humans.
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