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 specific35S-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 αld 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.
Objectif
Les médicaments agonistes des récepteurs alphaadrénergiques (AR) (par ex., l’épinéphrine) sont communément utilisés lors des interventions sur les voies aériennes supérieures, afin de rétrécir la muqueuse, de retarder l’absorption d’agents anesthésiques locaux et d’améliorer la visualisation en limitant l’hémorragie. Un traitement décongestionnant inclut également souvent des agents agonistes αAR; toutefois, la surutilisation de ces médicaments (par ex., l’oxymétazoline) peut engendrer une rhinite chronique et l’augmentation rebond des sécrétions nasales lors de la cessation du traitement. Puisque les décongestionnants actuels stimulent les αAR de manière non-sélective, la caractérisation de la distribution des sous-types d’αAR dans les voies aériennes de l’homme (cornet nasal) offre la possibilité de perfectionner les cibles thérapeutiques tout en minimisant les effets secondaires. C’est pourquoi nous avons examiné l’expression des sous-types d’αAR au niveau du cornet nasal humain dans les cellules épithéliales, du canal, des glandes et des vaisseaux, à l’aide d’une hybridation in situ.
Méthode
étant donné que des anticorps anti-récepteurs sensibles et spécifiques ainsi que des ligands très sélectifs des sous-types d’αAR sont disponibles actuellement, l’hybridation in situ a été effectuée sur des sections de trois échantillons de cornet nasal humain afin d’identifier la distribution d’ARN messager des sous-types d’αAR. Des sondes d’ARN messager marquées au35S et spécifiques au sous-type ont été incubées avec des sections de cornet nasal, et les fragments protégés restants après le traitement à la ribonucléase ont été analysés par microscopie optique et sur fond noir.
Résultats
Dans les tissus non-vasculaires, l’ARN messager AR αld est prédominant, alors que le α2c est notablement le seul sous-type d’αAR présent dans les sinusoïdes et les anastomoses artérioveineuses.
Conclusion
On considère maintenant que la constriction des sinus nasaux médiée par AR est à la base des thérapies de décongestion qui minimisent les sécrétions et rapetissent les tissus lors des interventions sur les voies aériennes. Ces résultats suggèrent donc que les sous-types d’AR α2c fournissent une nouvelle cible sélective pour les traitements de décongestion chez les humains.
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Stafford-Smith, M., Wilson, K., Bartz, R. et al. Alpha-adrenergic mRNA subtype expression in the human nasal turbinate. Can J Anesth 54, 549–555 (2007). https://doi.org/10.1007/BF03022319
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DOI: https://doi.org/10.1007/BF03022319