Lemmer B, Carlebach R, Stiller M, Ohm T G, Nitsch R
Zentrum der Pharmakologie, J.W. Goethe-Universität, Frankfurt, F.R.G.
Brain Res. 1991 Nov 29;565(2):225-30. doi: 10.1016/0006-8993(91)91653-i.
In rat hippocampal tissue the basal as well as drug-stimulated adenylate cyclase (AC) activity was studied after sacrificing the animals at 9 different circadian times (01.00, 04.00, 07.00, 10.00, 13.00, 16.00, 19.00, 22.00, 01.00 h). The AC was stimulated in vitro either via the beta-adrenoceptor by isoprenaline (IPN, 0.01-100 mumol/l plus GTP 0.005-50 mumol/l, via the GTP-binding protein by Gpp(NH)p (0.03-100 mumol/l) or via the catalytic unit of the AC by forskolin (0.1-600 mumol/l). For each drug dose-response curves could be constituted in single hippocampal tissues at each of the time points of sacrifice. Whereas maximal stimulation by forskolin was not achieved with the highest dose used (600 mumol/l, EC50-, Emax-values and Hill-coefficients could be calculated for both IPN and Gpp(NH)p, respectively. Thus, the rank order of drug stimulated AC activity was forskolin > Gpp(NH)p > IPN. However, no circadian phase-dependency in basal as well as drug-stimulated AC activity was found.
在大鼠海马组织中，于9个不同的昼夜节律时间点（01:00、04:00、07:00、10:00、13:00、16:00、19:00、22:00、01:00时）处死动物后，研究了基础以及药物刺激的腺苷酸环化酶（AC）活性。AC在体外通过异丙肾上腺素（IPN，0.01 - 100 μmol/L加GTP 0.005 - 50 μmol/L）经β - 肾上腺素能受体刺激，通过Gpp(NH)p（0.03 - 100 μmol/L）经GTP结合蛋白刺激，或通过福斯高林（0.1 - 600 μmol/L）经AC的催化单位刺激。对于每种药物，在每个处死时间点的单个海马组织中均可构建剂量反应曲线。虽然使用的最高剂量（600 μmol/L）未达到福斯高林的最大刺激效果，但分别针对IPN和Gpp(NH)p计算了EC50、Emax值和希尔系数。因此，药物刺激AC活性的顺序为福斯高林>Gpp(NH)p>IPN。然而，未发现基础及药物刺激的AC活性存在昼夜节律相位依赖性。
