Ruffolo R R, Sulpizio A C, Nichols A J, DeMarinis R M, Hieble J P
Department of Pharmacology, Smith Kline & French Laboratories, King of Prussia, PA 19406-0939.
Naunyn Schmiedebergs Arch Pharmacol. 1987 Oct;336(4):415-8. doi: 10.1007/BF00164875.
Most alpha 2-adrenoceptor antagonists do not discriminate between pre- and postjunctional alpha 2-adrenoceptors, and this has led to the commonly held belief that pre- and postjunctional alpha 2-adrenoceptors may represent one homogeneous population of receptors. SK&F 104078 has been shown to be a potent antagonist at postjunctional alpha 2-adrenoceptors at concentrations that do not block prejunctional alpha 2-adrenoceptors. Thus, SK&F 104078 is a competitive postjunctional alpha 2-adrenoceptor antagonist in canine and rabbit saphenous veins, canine saphenous artery and human platelet with a dissociation constant of approximately 100 nmol/l. Conversely, SK&F 104078 is inactive as a prejunctional alpha 2-adrenoceptor antagonist in atria from dog, guinea pig, rabbit and rat, and in guinea-pig ileum at concentrations up to 10,000 nmol/l. Likewise, SK&F 104078 has the ability to block postjunctional arterial alpha 2-adrenoceptors in vivo in the pithed rat at doses that do not inhibit prejunctional alpha 2-adrenoceptors in the same model. The results suggest that pre- and postjunctional alpha 2-adrenoceptors may not represent one homogeneous class, but rather are discrete subtypes of the alpha 2-adrenoceptor that may be differentiated by SK&F 104078.
大多数α2 - 肾上腺素能受体拮抗剂无法区分突触前和突触后α2 - 肾上腺素能受体，这导致人们普遍认为突触前和突触后α2 - 肾上腺素能受体可能代表同一类均一的受体群体。已证明SK&F 104078在不阻断突触前α2 - 肾上腺素能受体的浓度下，是突触后α2 - 肾上腺素能受体的强效拮抗剂。因此，在犬和兔的隐静脉、犬隐动脉及人血小板中，SK&F 104078是一种竞争性突触后α2 - 肾上腺素能受体拮抗剂，其解离常数约为100 nmol/l。相反，在犬、豚鼠、兔和大鼠的心房以及豚鼠回肠中，当浓度高达10,000 nmol/l时，SK&F 104078作为突触前α2 - 肾上腺素能受体拮抗剂无活性。同样，在去大脑大鼠体内，SK&F 104078在不抑制同一模型中突触前α2 - 肾上腺素能受体的剂量下，能够阻断突触后动脉α2 - 肾上腺素能受体。结果表明，突触前和突触后α2 - 肾上腺素能受体可能并非代表同一类均一的类型，而是α2 - 肾上腺素能受体的不同亚型，SK&F 104078可能可以区分它们。
