title: Alpha-2c-adrenergic receptors contribute to basal nasal patency in the anesthetized cat.
abstract: BACKGROUND
  Nasal congestion is the most troublesome symptom associated with a variety of upper airway diseases, including allergic rhinitis and the common cold. A better understanding of the mechanisms that regulate nasal cavity caliber may engender the development of novel treatment strategies. It is well accepted that alpha-adrenergic (both alpha(1) and alpha(2)) mechanisms play a fundamental role in the control and maintenance of basal nasal patency. JP-1302 is a selective alpha(2c)-subtype antagonist that has been recently described in the scientific literature. Thus, we sought to examine the potential effects of this new pharmacological tool on basal nasal patency.
  
  
  METHODS
  Using acoustic rhinometry, we studied the activity of the selective alpha(2c)-antagonist JP-1302 on nasal cavity volumes in an anesthetized cat. Cumulative concentrations of JP-1302 were applied directly into the right nasal cavity. Changes in the nasal cavity geometry of the drug-treated naris relative to the untreated left nasal cavity were determined. In separate studies, the nonselective alpha(2)-antagonist yohimbine and the nonselective alpha(1)-antagonist prazosin were run as comparators. Systolic blood pressure was measured at the hind leg, using an ultrasonic Doppler flow detector.
  
  
  RESULTS
  JP-1302 (0.03, 0.1, 0.3 and 1.0%) administered by the intranasal route decreased nasal cavity volumes from baseline values by 17, 25, 40 and 40%, respectively. Yohimbine (0.03, 0.1, 0.3 and 1.0%) decreased volumes by 19, 36, 46 and 53%, and topical administration of the nonselective alpha(1)-antagonist prazosin (0.001, 0.003, 0.01, 0.03 and 0.1%) decreased volumes by 6, 47, 56, 64 and 71%, respectively. JP-1302, yohimbine and prazosin, at the dose level tested, did not alter the blood pressure.
  
  
  CONCLUSIONS
  The present set of experiments indicates that both alpha(1)- and alpha(2)-adrenergic receptors are involved in the maintenance of basal nasal patency in the cat. Moreover, alpha(2c)-receptors may play a significant role in the sympathetic control of upper airway function.
authors.affiliation: Department of Neurobiology/Respiratory, Schering-Plough Research Institute, Kenilworth, N.J. 07033-0539, USA.
authors.forename: Garfield G
authors.initials: GG
authors.lastname: Mingo
authors.forename: Michel R
authors.initials: MR
authors.lastname: Corboz
authors.forename: Brian G
authors.initials: BG
authors.lastname: Salisbury
authors.forename: Kevin D
authors.initials: KD
authors.lastname: McCormick
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Boyce
authors.forename: Gitali
authors.initials: G
authors.lastname: Mukhopadhyay
authors.forename: Robbie L
authors.initials: RL
authors.lastname: McLeod
mesh_terms: D000166:Acridines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000281:Administration, Intranasal; D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004305:Dose-Response Relationship, Drug; D008297:Male; D009296:Nasal Cavity / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012220:Rhinitis / Q000188:drug therapy; D023842:Rhinometry, Acoustic; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D000166:Acridines; D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; C518829:JP-1302; D010879:Piperazines; D020033:Protein Isoforms; D018341:Receptors, Adrenergic, alpha-2