alpha(1)-adrenoceptor subtypes and effect of alpha(1A)-adrenoceptor agonist NS-49 on guinea pig nasal mucosa vasculature.
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.
Tanimitsu
N
N
Department of Otorhinolaryngology, Hiroshima University School of Medicine, Minami-ku, Hiroshima, Japan.
Yajin
K
K
Sasa
M
M
Tsuru
H
H
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009297:Nasal Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010109:Oxymetazoline / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D013134:Spiperone / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
C092989:3'-(2-amino-1-hydroxyethyl)-4'-fluoromethanesulfonanilide; D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000813:Anilides; D004146:Dioxanes; D010879:Piperazines; C057446:5-methylurapidil; D015016:Yohimbine; C051731:chlorethylclonidine; D013134:Spiperone; D010109:Oxymetazoline; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; C053428:BMY 7378; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin