Eltze M
Department of Pharmacology, Byk Gulden, Konstanz, Germany.
Eur J Pharmacol. 1996 Sep 12;311(2-3):187-98. doi: 10.1016/0014-2999(96)00430-x.
alpha 1-Adrenoceptor agonists ((-)-adrenaline = (-)-noradrenaline > > L-phenylephrine > methoxamine > (-)-(4a R, 10a R)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9-methylthio-2 H-naphth[2,3-b]-1,4-oxazine (SDZ NVI 085) > cirazoline) evoked contraction of isolated mouse spleen strips, whereas oxymetazoline and indanidine were nearly inactive. Splenic contractions elicited by (-)-noradrenaline were inhibited by chloroethylclonidine (3 x 10(-6) - 6 x 10(-5) M) and partially attenuated by SZL-49 (10(-7) -10(-6) M), but remained resistant to (+/-)-isradipine (10(-9) -10(-7) M). The contractions were competitively antagonized by low concentrations of the alpha 1B-adrenoceptor-selective antagonist, spiperone (pA2 = 8.29), but by relatively high concentrations of the alpha 1A-adrenoceptor-selective receptor antagonists, tamsulosin (pA2 = 8.62), 5-methyl-urapidil (pA2 = 7.03), (+)-niguldipine (pA2 = 6.26) and the alpha 1D-adrenoceptor-selective antagonist, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro-[4.5]dec ane-7, 9-dione (BMY 7378) (pA2 = 6.76). Functional antagonist affinities at mouse spleen alpha 1-adrenoceptors were consistent with those at guinea-pig splenic alpha 1B-adrenoceptors, but not with those of either rat vas deferens alpha 1A- or rat aortic alpha 1D-adrenoceptors. Antagonist affinities at mouse spleen alpha 1-adrenoceptors correlated also best with published antagonist data on cloned and expressed alpha 1b-adrenoceptors but less well with those for either alpha 1a- or alpha 1d-adrenoceptors. The results provide pharmacological evidence that the alpha 1-adrenoceptor mediating smooth muscle contraction of mouse spleen is the B subtype.
α1肾上腺素受体激动剂（（-）-肾上腺素=（-）-去甲肾上腺素>>L-去氧肾上腺素>甲氧明>（-）-（4aR，10aR）-3,4,4a,5,10,10a-六氢-6-甲氧基-4-甲基-9-甲硫基-2H-萘并[2,3-b]-1,4-恶嗪（SDZ NVI 085）>西拉唑啉）可引起离体小鼠脾条收缩，而羟甲唑啉和茚达立定几乎无活性。（-）-去甲肾上腺素引起的脾收缩被氯乙可乐定（3×10^（-6） - 6×10^（-5）M）抑制，被SZL-49（10^（-7） - 10^（-6）M）部分减弱，但对（±）-伊拉地平（10^（-9） - 10^（-7）M）仍有抗性。低浓度的α1B肾上腺素受体选择性拮抗剂螺哌隆（pA2 = 8.29）可竞争性拮抗该收缩，但需要相对高浓度的α1A肾上腺素受体选择性拮抗剂坦索罗辛（pA2 = 8.62）、5-甲基-乌拉地尔（pA2 = 7.03）、（+）-尼鲁地平（pA2 = 6.26）以及α1D肾上腺素受体选择性拮抗剂8-[2-[4-（2-甲氧基苯基）-1-哌嗪基]乙基]-8-氮杂螺[4.5]癸烷-7,9-二酮（BMY 7378）（pA2 = 6.76）。小鼠脾α1肾上腺素受体的功能性拮抗剂亲和力与豚鼠脾α1B肾上腺素受体的一致，但与大鼠输精管α1A或大鼠主动脉α1D肾上腺素受体的不同。小鼠脾α1肾上腺素受体的拮抗剂亲和力也与已发表的关于克隆和表达的α1b肾上腺素受体的拮抗剂数据相关性最好，而与α1a或α1d肾上腺素受体的相关性较差。结果提供了药理学证据，表明介导小鼠脾平滑肌收缩的α1肾上腺素受体是B亚型。
