Effects of the neuropeptide Y (NPY)-receptor antagonist BIBP3226 on vascular NPY-receptors with different ligand requirements.
Effects of the neuropeptide Y (NPY)-receptor antagonist BIBP3226 on vascular NPY-receptors with different ligand requirements.
复制标题
神经肽 Y (NPY) 受体拮抗剂 BIBP3226 对具有不同配体需求的血管 NPY 受体的影响。
DOI：
10.1111/j.1600-0773.1996.tb00271.x
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
M. Ekelund
中科院分区：
文献类型：
--
作者：
L. Grundemar;M. Ekelund
目的是检查新开发的神经肽Y（NPY）受体拮抗剂BIBP 3226的作用，并分别表征离体豚鼠腔静脉和人皮下动脉中的NPY受体。BIBF 3226 ≤ 1 μ M不影响基础张力。用递增浓度的BIBF 3226（10 nM-1 μ M）预处理导致豚鼠腔静脉中Y1受体选择性激动剂[Pro 34]NPY的浓度-反应曲线进行性漂移。Schild图的回归分析得出pA 2值为7.58（7.20-8.33，95%置信区间），回归线斜率为0.96（0.52-1.39，95%置信区间），相关系数为0.78。NPY和C-末端NPY 2-36诱发等效浓度依赖性收缩，两者均对BIBF 3226敏感。尽管比NPY 2-36效力低，但由NPY 5-36诱导的收缩也被BIBP 3226拮抗。在人皮下动脉中，[Pro 34]NPY而不是NPY 2-36（≤ 0.3 μ M）引起浓度依赖性收缩。用BIBF 3226（0.1 μ M）预处理导致[Pro 34]NPY的浓度-反应曲线从7.38 +/- 0.10移动到6.95 +/- 0.16（P < 0.05，n = 6）。本研究表明，Y1受体选择性拮抗剂BIBP 3226分别在豚鼠腔静脉和人皮下动脉中有效拮抗具有不同配体需求的血管NPY受体。看来，豚鼠Y1-受体是严格的要求比人Y1-受体的N-末端部分的NPY。
The aim was to examine effects of a newly developed neuropeptide Y (NPY)-receptor antagonist, BIBP3226 and to characterize NPY-receptors in the isolated guinea pig caval vein and human subcutaneous artery, respectively. BIBP3226 < or = 1 microM did not affect the basal tension. Pretreatment with increasing concentrations of BIBP3226 (10 nM-1 microM) resulted in a progressive rightward shift of the concentration-response curve to the Y1-receptor selective agonist [Pro34]NPY in the guinea pig caval vein. Regression analysis of the Schild plot gave a pA2-value of 7.58 (7.20-8.33, 95% confidence interval), slope of regression line 0.96 (0.52-1.39, 95% confidence interval) and a correlation coefficient of 0.78. NPY and the C-terminal NPY 2-36 evoked equipotent concentration-dependent contractions, both of which were sensitive to BIBP3226. Although less potent than NPY 2-36, also the contraction induced by NPY 5-36 was antagonized by BIBP3226. In the human subcutaneous artery [Pro34]NPY but not NPY 2-36 (< or = 0.3 microM) evoked a concentration-dependent contraction. Pretreatment with BIBP3226 (0.1 microM) resulted in a rightward shift of the concentration-response curve to [Pro34]NPY (from 7.38 +/- 0.10 to 6.95 +/- 0.16 (P < 0.05, n = 6). The present study has shown that the Y1-receptor-selective antagonist BIBP3226 potently antagonizes vascular NPY-receptors with different ligand requirements in the guinea pig caval vein and human subcutaneous artery, respectively. It appears that the guinea pig Y1-receptor is much less stringent in its demand on the N-terminal part of NPY than that of human Y1-receptors.