交互的3-benzodiazepines和cyclothiazide AMPA受体:膜片箝记录培养的神经元,在海马CA1区片。

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兰姆G, Swandulla D, Collingridge GL,哈特曼年代,帕森斯CG

交互的3-benzodiazepines和cyclothiazide AMPA受体:膜片箝记录培养的神经元,在海马CA1区片。

Br J杂志。1996年3月,117(6):1209 - 21所示。

PubMed ID

8882618 (在PubMed

]

文摘

1。52466年,3-benzodiazepines GYKI GYKI引起53405年和53655年GYKI AMPA-induced电流在培养上丘神经元非use-dependent方式(稳态IC50s: GYKI 52466 9.8 + / - 0.6 microM;GYKI 53405 3.1 + / - 0.6 microM;GYKI 53655 0.8 + / - 0.1 microM)。2。更高浓度的三个对手爆发放缓动力学和加快了抵消AMPA-induced动力学电流指示性的变构与AMPA的交互识别网站。3所示。Cyclothiazide microM(3 - 300)大幅放缓的脱敏AMPA-induced水流和强稳态电流(EC50 10.0 + / - 2.5 microM)在更大程度上比峰值电流。两τ和τ也增加了cyclothiazide浓度的方式(EC50: 42.1 + / - 4.5 microMτ;31.6 + / - 6.6 microM)τ。 4. Cyclothiazide (10-100 microM) shifted the concentration-response curves of the 2,3-benzodiazepines to the right. For example, with 10 microM cyclothiazide the IC50s of GYKI 52466 and GYKI 53405 on steady-state AMPA-induced currents were 57.9 +/- 9.5 and 41.6 +/- 1.5 microM, respectively. 5. GYKI 53405 and GYKI 52466 concentration-dependently reversed the effects of cyclothiazide (100 microM) on offset kinetics (GYKI 53405 IC50 16.6 +/- 4.2 microM). However, the 2,3-benzodiazepines were unable to reintroduce desensitization in the presence of cyclothiazide and even concentration-dependently slowed the onset kinetics of AMPA responses further (GYKI 53405 EC50 8.0 +/- 2.8 microM). 6. GYKI 52466 decreased the peak amplitude of hippocampal area CA1 AMPA receptor-mediated excitatory postsynaptic currents (e.p.s.cs) (IC50 10.8 +/- 0.8 microM) with no apparent effect on response kinetics. Cyclothiazide prolonged the decay time constant of AMPA receptor-mediated e.p.s.cs (EC50 35.7 +/- 6.5 microM) with less pronounced effects in slowing e.p.s.c. onset kinetics and increasing e.p.s.c. amplitude. 7. Cyclothiazide (330 microM) shifted the concentration-response curve for the effects of GYKI 52466 on AMPA receptor-mediated e.p.s.c. peak amplitude to the right (GYKI 52466 IC50 26.9 +/- 9.4 microM). Likewise, GYKI 52466 (30-100 microM)) shifted the concentration-response curve for the effects of cyclothiazide on AMPA receptor-mediated e.p.s.c. decay time constants to the right. 8. In conclusion, cyclothiazide and the 2,3-benzodiazepines seem to bind to different sites on AMPA receptors but exert strong allosteric interactions with one another and with other domains such as the agonist recognition site. The interactions of GYKI 52466 and cyclothiazide on AMPA receptor-mediated e.p.s.cs in area CA1 of hippocampal slices provide evidence that the decay time constant of these synaptic events are not governed by desensitization.

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药物靶点

药物	目标	类	生物	药理作用	行动
Cyclothiazide	碳酸酐酶1	蛋白质	人类	未知的	抑制剂	细节