Lemmer B, Lang P H
Center of Pharmacology, J.W. Goethe-University, Frankfurt/M., Federal Republic of Germany.
Chronobiol Int. 1984;1(3):217-23. doi: 10.3109/07420528409063898.
Binding studies with the beta-adrenoceptor antagonist ligand [3H]-dihydroalprenolol ([3H]-DHA, spec. act, 90-102 Ci/mmol) were performed with ventricular membranes L-D-synchronized (L:0.7-19 hr, D:-07 hr) male rats, sacrificed either at 08 hr or at 20 hr. Saturation experiments with crude or washed and preincubated membranes revealed two affinity states of specific [3H]-DHA binding which were abolished after addition of the guanine nucleotide Gpp(NH)p. In crude membranes the apparent Bmax-value at 20 hr was about 40% higher than at 08 hr, in washed and preincubated membranes the nocturnal increase in the apparent Bmax-value was not observed. Pretreatment of rats with isoprenaline (50 mg/kg, i.p.) decreased and catecholamine depletion (reserpine plus inhibition of tyrosine-hydroxylase) increased Bmax-values in crude membranes. The circadian-stage-dependent and the drug-induced effects on the apparent number of beta-adrenoceptors are assumed to be due to circadian or drug-induced variations in the turnover of cardiac noradrenaline.
采用β-肾上腺素能受体拮抗剂配体[3H]-二氢阿普洛尔（[3H]-DHA，比活度为90 - 102 Ci/mmol），对L-D同步化（L：0.7 - 19小时，D：-0.7小时）的雄性大鼠心室膜进行结合研究，这些大鼠于08时或20时处死。对粗制膜或洗涤并预孵育后的膜进行饱和实验，结果显示特异性[3H]-DHA结合存在两种亲和力状态，添加鸟嘌呤核苷酸Gpp(NH)p后这两种状态消失。在粗制膜中，20时的表观Bmax值比08时约高40%；在洗涤并预孵育后的膜中，未观察到表观Bmax值的夜间增加。用异丙肾上腺素（50 mg/kg，腹腔注射）预处理大鼠会降低粗制膜中的Bmax值，而去甲肾上腺素耗竭（利血平加酪氨酸羟化酶抑制）则会增加粗制膜中的Bmax值。昼夜节律阶段依赖性以及药物对β-肾上腺素能受体表观数量的影响，被认为是由于心脏去甲肾上腺素周转的昼夜节律变化或药物诱导的变化所致。
