Jacques D, Cadieux A, Dumont Y, Quirion R
Douglas Hospital Research Centre, Faculty of Medicine, McGill University, Verdun, Québec, Canada.
Eur J Pharmacol. 1995 May 4;278(1):R3-5. doi: 10.1016/0014-2999(95)00179-o.
The newly developed, purported non-peptide neuropeptide Y Y1 receptor antagonist BIBP3226 was evaluated for its potential effect on the recently characterized Y3 receptor subtype and for its apparent affinity in rat and human brain membrane binding assays using highly selective neuropeptide Y Y1 and Y2 radioligands. BIBP3226 potently blocked (pA2 = 7.36) the contractile effect of neuropeptide Y in the rabbit saphenous vein, a Y1 receptor bioassay and demonstrated nM affinity for Y1/[125I][Leu31,Pro34]peptide YY binding sites. In contrast, it failed to antagonize the biological effects of neuropeptide Y in the rat vas deferens (Y2) and rat colon (Y3) and did not significantly competed for Y2/[125I]peptide YY-(3-36) binding sites in rat and human brain homogenates. Taken together, the results demonstrate further the high potency and selectivity of BIBP3226 for the neuropeptide Y Y1 receptor by establishing its lack of antagonist activity on the Y3 subtype.
对新开发的、据称是非肽类的神经肽Y Y1受体拮抗剂BIBP3226，利用高选择性神经肽Y Y1和Y2放射性配体，在大鼠和人脑膜结合试验中评估了其对最近鉴定的Y3受体亚型的潜在作用及其表观亲和力。BIBP3226在兔隐静脉（一种Y1受体生物测定法）中能有效阻断（pA2 = 7.36）神经肽Y的收缩作用，并对Y1/[125I][Leu31,Pro34]肽YY结合位点表现出纳摩尔级亲和力。相比之下，它未能拮抗大鼠输精管（Y2）和大鼠结肠（Y3）中神经肽Y的生物学效应，并且在大鼠和人脑匀浆中对Y2/[125I]肽YY-(3 - 36)结合位点没有明显的竞争作用。综上所述，这些结果通过证实BIBP3226对Y3亚型缺乏拮抗活性，进一步证明了其对神经肽Y Y1受体的高效力和选择性。
