Analysis for the physiological role of a novel GABAィイD2AィエD2 receptor sub-class.

早些时候，我们揭示了非常高和高度亲和力的结合网站的存在。在阿米格达拉的价值观就是这样。0.4 and 18.7 nM， respectively） in the aminobutyric acid/benzodiazepine （GABA D2A/BZ） receptor in the living monkey brain by an in vivo saturation study using D111/D1C-labeled Ro15-4513 with high specific radioactivity （>70 GBq/？mol）。To assess the physiological function of the very high-affinity binding sites of GABA-D2A-D2/Benzodiazepine （BZ） receptor in the intact living brain， the binding of a-D111C-labeled BZ partial inverse agonist （[-D11C]Ro15-4513） of the GABA-D2A-D2/BZ receptor was investigated by the positron emManagement tomography （PET） with conscious and anesthetized monkeys。在有意识的猴子、睡眠剥夺或氯胺酮中，一个NMDA受体阻断器，治疗增加了[EYD 111 EYD 1C] Ro 15 -4513的绑定，但没有[EYD 111 EYD 1C] Ro 15 -1788的绑定。Furthermore， propofol， a positive allosteric modulator of the GABA D2A y D2/BZ receptors， anesthesia induced decreases in the binding of [y D111 y D1C] Ro15-4513 but not did that of [y D111 y D1C]Ro15-1788。very high affinity binding sites of [イイD111エD1C]Ro15-4513 were invisible in the most of limbic regions under the propofol anesthesia。These results strongly indicate that the binding？teristics of the [イイD111エD1C]Ro15-4513 in vivo may be related to both the heterogeneity of GABAイD2AエD2/BZ receptor and its efficacy modulated by allosteric agents in the living brain。

Previously, we revealed the presence of very high- and high-affinity binding sites (ex. Kd values in the amygdala are ca. 0.4 and 18.7 nM, respectively) in the γ-aminobutyric acid/benzodiazepine (GABAィイD2AィエD2/BZ) receptor in the living monkey brain by an in vivo saturation study using ィイD111ィエD1C-labeled Ro15-4513 with high specific radioactivity (>70 GBq/μmol). To assess the physiological function of the very high-affinity binding sites of GABAィイD2AィエD2/Benzodiazepine (BZ) receptor in the intact living brain, the binding of a ィイD111ィエD1C-labeled BZ partial inverse agonist ([ィイD111ィエD1C]Ro15-4513) of the GABAィイD2AィエD2/BZ receptor was investigated by the positron emission tomography (PET) with conscious and anesthetized monkeys. In the conscious monkey, sleep deprivation or ketamine, a NMDA receptor blocker, treatment increased the binding of [ィイD111ィエD1C]Ro15-4513, but not did that of [ィイD111ィエD1C]Ro15-1788. Furthermore, propofol, a positive allosteric modulator of the GABAィイD2AィエD2/BZ receptors, anesthesia induced decreases in the binding of [ィイD111ィエD1C]Ro15-4513 but not did that of [ィイD111ィエD1C]Ro15-1788. The very high affinity binding sites of [ィイD111ィエD1C]Ro15-4513 were invisible in the most of limbic regions under the propofol anesthesia. These results strongly indicate that the binding characteristics of the [ィイD111ィエD1C]Ro15-4513 in vivo may be related to both the heterogeneity of GABAィイD2AィエD2/BZ receptor and its efficacy modulated by allosteric agents in the living brain.