Gascón S, Dierssen M, Màrmol F, Vivas N M, Badia A
Departament de Farmacologia i Psiquiatria, Universitat Autònoma de Barcelona, Spain.
J Pharm Pharmacol. 1993 Oct;45(10):907-9. doi: 10.1111/j.2042-7158.1993.tb05618.x.
The effects of ageing on alpha 1-adrenoceptor subtypes have been examined in heart ventricular muscle of young (2-3 months) and middle-aged (18 months) Sprague-Dawley rats. Radioligand binding studies with [3H]prazosin revealed an age-related loss of binding sites (Bmax 56.7 +/- 1.93 fmol (mg protein)-1 age 2 months vs 31.7 +/- 2.45 fmol (mg protein)-1 age 18 months) not followed by changes in the dissociation constant value (Kd 0.16 +/- 0.03 nM age 2 months and 0.10 +/- 0.03 nM age 18 months). Competition curves with WB 4101 showed two distinct sites with different affinities, the proportion of sites with high affinity being similar for both age groups (22.2 +/- 1.89% vs 17.8 +/- 1.96% for animals aged 2 and 18 months, respectively). Agonist displacement curves of [3H]prazosin indicate the existence of two different affinity sites for the agonist, that are maintained regardless of the ageing process (R(high) = 16.2 +/- 1.54% and R(low) = 83.8 +/- 1.89% in rats aged 2 months and R(high) = 16.3 +/- 3.23% and R(low) = 83.7 +/- 3.95% in rats aged 18 months). The fractional inactivation of alpha 1-adrenoceptors by chloroethylclonidine resulted in a loss of [3H]prazosin specific binding, and a percentage of 22.5 +/- 0.95 and 22.6 +/- 4.2 of remaining binding sites for the groups of 2 and 18 months of age, respectively. The percentage of chloroethylclonidine-insensitive [3H]prazosin binding sites was similar to those with high affinity for WB4101. The present study confirms a decline of alpha 1-adrenoceptors with increasing age and reveals that the equilibrium of the expression of the two existing subpopulations of the receptor is maintained during ageing.
研究了衰老对年轻（2 - 3个月）和中年（18个月）Sprague-Dawley大鼠心室肌α1 -肾上腺素能受体亚型的影响。用[3H]哌唑嗪进行的放射性配体结合研究显示，结合位点存在与年龄相关的减少（2个月龄时Bmax为56.7±1.93 fmol（mg蛋白）-1，18个月龄时为31.7±2.45 fmol（mg蛋白）-1），但解离常数（Kd）值无变化（2个月龄时Kd为0.16±0.03 nM，18个月龄时为0.10±0.03 nM）。用WB 4101进行的竞争曲线显示有两个具有不同亲和力的不同位点，高亲和力位点的比例在两个年龄组中相似（2个月龄动物分别为22.2±1.89%和18个月龄动物为17.8±1.96%）。[3H]哌唑嗪的激动剂置换曲线表明激动剂存在两个不同亲和力的位点，且无论衰老过程如何均保持不变（2个月龄大鼠中R(高)=16.2±1.54%，R(低)=83.8±1.89%；18个月龄大鼠中R(高)=16.3±3.23%，R(低)=83.7±3.95%）。氯乙可乐定对α1 -肾上腺素能受体的部分失活导致[3H]哌唑嗪特异性结合丧失，2个月龄组和18个月龄组剩余结合位点的百分比分别为22.5±0.95和22.6±4.2。对氯乙可乐定不敏感的[3H]哌唑嗪结合位点的百分比与对WB4101具有高亲和力的位点相似。本研究证实随着年龄增长α1 -肾上腺素能受体减少，并揭示在衰老过程中受体两个现有亚群表达的平衡得以维持。
