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 guin ea pig nasal mucosa was suspended in an organ bath containing Krebs' bicarb onate solution. Changes in tension were recorded isometrically. Concentrati on-response curves for agonists were obtained in a cumulative manner. Norad renaline 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 putat ive alpha(1A)-adrenoceptor antagonists WB-4101 (2-(2,6-dimethoxyphenoxyethy l)aminomethyl-1,4-benzodioxane) and 5-methyl-urapidil antagonized the respo nse to noradrenaline competitively (pA(2) for prazosin < 9.0). Conversely, putative alpha(1B) and alpha(1D)-adrenoceptor antagonists (spiperone and BM Y7378 (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) (o r alpha(1N))subtype may also be present in the guinea pig nasal mucosa vasc ulature. Furthermore, NS-49 might prove to be a nasal mucosa vasoconstricto r, which will improve nasal obstruction (C) 2000 Elsevier Science B.V. All rights reserved.