alpha(1)-adrenoceptor subtypes and effect of alpha(1A)-adrenoceptor agonist NS-49 on guinea pig nasal mucosa vasculature.

Abstract

It is now clear that alpha(1)-adrenoceptors comprise a heterogeneous family. In the present study, we characterized the alpha(1)-adrenoceptor subtype in the nasal mucosa vasculature of guinea pigs. A rectangular strip of guinea pig nasal mucosa was suspended in an organ bath containing Krebs' bicarbonate solution. Changes in tension were recorded isometrically. Concentration-response curves for agonists were obtained in a cumulative manner. Noradrenaline produced the greatest contraction of the nasal mucosa vasculature. NS-49 ((R)-(-)-3'-(2-amino-1-hydroxyethyl)-4'-fluoromethane sulfonanilide hydrochloride) and oxymetazoline worked as partial agonists. The intrinsic activities of NS-49 and oxymetazoline were 0.50+/-0.22 and 0.29+/-0.17, respectively, compared with noradrenaline (=1.00). Prazosin and the putative alpha(1A)-adrenoceptor antagonists WB-4101 (2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane) and 5-methylurapidil antagonized the response to noradrenaline competitively (pA(2) for prazosin<9.0). Conversely, putative alpha(1B) and alpha(1D)-adrenoceptor antagonists (spiperone and BMY7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4, 5]decane-7,9-dione), respectively) did not antagonize competitively. These results suggest that the alpha(1A)-subtype is predominant and that the alpha(1L) (or alpha(1N)) subtype may also be present in the guinea pig nasal mucosa vasculature. Furthermore, NS-49 might prove to be a nasal mucosa vasoconstrictor, which will improve nasal obstruction.

• Authors: N Tanimitsu, K Yajin, M Sasa, H Tsuru
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 387 Issue 1 Pg. 73-8 (Jan 03 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10633163 (Publication Type: Journal Article)

Chemical References

• 3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide
• Adrenergic alpha-1 Receptor Agonists
• Adrenergic alpha-Agonists
• Adrenergic alpha-Antagonists
• Anilides
• Dioxanes
• Piperazines
• 5-methylurapidil
• Yohimbine
• chlorethylclonidine
• Spiperone
• Oxymetazoline
• (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
• BMY 7378
• Clonidine
• Norepinephrine
• Prazosin

Topics

• Adrenergic alpha-1 Receptor Agonists
• Adrenergic alpha-Agonists (pharmacology)
• Adrenergic alpha-Antagonists (pharmacology)
• Anilides (pharmacology)
• Animals
• Blood Vessels (drug effects, physiology)
• Clonidine (analogs & derivatives, pharmacology)
• Dioxanes (pharmacology)
• Dose-Response Relationship, Drug
• Female
• Guinea Pigs
• In Vitro Techniques
• Male
• Nasal Mucosa (blood supply, drug effects, physiology)
• Norepinephrine (pharmacology)
• Oxymetazoline (pharmacology)
• Piperazines (pharmacology)
• Prazosin (pharmacology)
• Spiperone (pharmacology)
• Vasoconstriction (drug effects)
• Yohimbine (pharmacology)