BE 2254对突触后α-肾上腺素能受体的优先阻断作用。

Preferential blockade of postsynaptic alpha-adrenoceptors by BE 2254.

作者信息

Göthert M, Nolte J, Weinheimer G

出版信息

Eur J Pharmacol. 1981 Mar 5;70(1):35-42. doi: 10.1016/0014-2999(81)90429-5.

Abstract

The effects of 2-[beta-(4-hydroxyphenyl)-ethyl-aminomethyl]-tetralone (BE 2254) on pre- and postsynaptic alpha-adrenoceptors were studies in isolated rabbit hearts and strips of rabbit pulmonary arteries. The KCl (80 mM)-evoked output of endogenous noradrenaline from perfused hearts was significantly increased by BE 2254 (10(-7)-10(-6) M). The inhibitory effect of clonidine (10(-7) M) on KCl-evoked noradrenaline output was antagonized by BE 2254 (10(-6) and 10(-5) M) indicating that the compound causes a blockade of presynaptic alpha-adrenoceptors. In superfused pulmonary arteries, BE 2254 produced a parallel shift to the right of the concentration-response curve for noradrenaline: increasing effect on tension, pA2 = 8.75. The electrically (2 Hz) evoked 3H overflow from arteries preincubated with 3H-noradrenaline was increased by BE 2254 (3.2 x 10(-8)-3.2 x 10(-7) M). Considerably lower concentrations were sufficient to cause an inhibition of the electrically evoked increase in tension: 3.2 x 10(-9) M BE 2254 caused a 45% decrease. These results suggest that BE 2254, in spite of its rather high affinity to presynaptic alpha-adrenoceptors, preferentially blocks postsynaptic alpha-adrenoceptors.

摘要

在离体兔心和兔肺动脉条上研究了2-[β-(4-羟苯基)-乙基-氨基甲基]-四氢萘酮（BE 2254）对突触前和突触后α-肾上腺素能受体的作用。BE 2254（10⁻⁷ - 10⁻⁶ M）可显著增加KCl（80 mM）诱发的灌注心脏内源性去甲肾上腺素的释放量。BE 2254（10⁻⁶和10⁻⁵ M）拮抗可乐定（10⁻⁷ M）对KCl诱发的去甲肾上腺素释放的抑制作用，表明该化合物可阻断突触前α-肾上腺素能受体。在 superfused 肺动脉中，BE 2254使去甲肾上腺素的浓度-反应曲线平行右移：对张力的增强作用，pA2 = 8.75。BE 2254（3.2×10⁻⁸ - 3.2×10⁻⁷ M）可增加预先用³H-去甲肾上腺素孵育的动脉经电刺激（2 Hz）诱发的³H溢出。相当低的浓度就足以抑制电刺激诱发的张力增加：3.2×10⁻⁹ M BE 2254可使张力降低45%。这些结果表明，尽管BE 2254对突触前α-肾上腺素能受体具有相当高的亲和力，但它优先阻断突触后α-肾上腺素能受体。（注：文中superfused可能有误，推测是superfused，意为“超灌流的” ）