| Abstrakt: |
1 Pig nasal mucosal strips were incubated with α-adrenoceptor antagonists followed by α2-adrenoceptor agonist concentration–response curves. 2 Contractions elicited by the α2-adrenoceptor agonists BHT-920 (p D2 = 6.16 ± 0.07), UK 14,304 (p D2 = 6.89 ± 0.13) and PGE-6201204 (p D2 = 7.12 ± 0.21) were blocked by the α2-adrenoceptor antagonist yohimbine (0.1 μ m). In contrast, the α1-adrenoceptor antagonist prazosin (0.03 μ m) had no effect on the BHT-920-, UK 14,304- and PGE-6201204-induced contractions, but blocked the contractile response to the α1-adrenoceptor agonist phenylephrine (p D2 = 5.38 ± 0.04) and the mixed α1- and α2-adrenoceptor agonist oxymetazoline (p D2 = 6.30 ± 0.22). 3 The α2-adrenoceptor antagonist yohimbine (0.01–0.1 μ m, pA2 = 8.04), α2B/C-adrenoceptor antagonist ARC 239 (10 μ m, p Kb = 6.33 ± 0.21), α2A/C-adrenoceptor antagonist WB 4101 (0.3 μ m, p Kb = 8.01 ± 0.24), α2A-adrenoceptor antagonists BRL44408 (0.1 μ m, p Kb = 6.82 ± 0.34) and RX 821002 (0.1 μ m, p Kb = 8.31 ± 0.35), α2C-adrenoceptor antagonists spiroxatrine (1 μ m, p Kb = 7.32 ± 0.32), rauwolscine (0.1 μ m, p Kb = 8.16 ± 0.14) and HV 723 (0.3 μ m, p Kb = 7.68 ± 0.14) inhibited BHT-920-induced contractions in pig nasal mucosa. 4 The present antagonist potencies showed correlations with binding affinity estimates (p Ki) obtained for these antagonists at the human recombinant α2A- and α2C-adrenoceptors ( r = 0.78 and 0.83, respectively) and with binding affinity estimates (p Kd) obtained in pig native α2A- and α2C-monoreceptor assays ( r = 0.85 and 0.78, respectively). No correlation was observed for the α2B-subtype. 5 In conclusion, contractile responses to phenylephrine, BHT-920, UK 14,304, PGE-6201204 and oxymetazoline indicate that α1- and α2-adrenoceptors are present and mediate vasoconstriction in pig nasal mucosa. Furthermore, correlation analysis comparing antagonist potency in pig nasal mucosa with affinities for human recombinant α2-adrenoceptors and native pig α2-adrenoceptors suggest that α2A- and α2C-adrenoceptor subtypes constrict pig nasal mucosa vasculature. [ABSTRACT FROM AUTHOR] |
