Autoradiographic localization and biochemical characterization of peripheral type CCK receptors in rat CNS using highly selective nonpeptide CCK antagonists
Autoradiographic localization and biochemical characterization of peripheral type CCK receptors in rat CNS using highly selective nonpeptide CCK antagonists
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使用高选择性非肽 CCK 拮抗剂对大鼠 CNS 中外周型 CCK 受体进行放射自显影定位和生化表征
DOI：
10.1523/jneurosci.07-09-02967.1987
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发表时间：
1987
期刊：
影响因子：
--
通讯作者：
G. Woodruff
中科院分区：
文献类型：
--
作者：
D. Hill;N. Campbell;T. M. Shaw;G. Woodruff
用两种有效的高选择性非肽类拮抗剂L-365，031 [1-甲基-3-（4-溴苯甲酰基）氨基-5-苯基-3H-1，4-苯并二氮杂卓-2-酮]和3 H-L-364，718 [1-甲基-3-（2-吲哚啉酰基）氨基-5-苯基-3H-1，4-苯并二氮杂卓-2-酮]定位大鼠脑内的“外周”CCK受体。在放射自显影实验中，L-365，031取代了脚间核（IPN）（IC 50 = 7 × 10（-8）M）、最后区（AP）和孤束核（NTS）的125 I-博尔顿亨特CCK-8结合，而不影响与其他区域（如大脑皮层或三叉神经脊束）的特异性结合。去硫酸化CCK优先抑制125 I-CCK与大脑皮层的结合（IC 50 = 7 × 10（-8）M），而不是IPN（IC 50大于1 × 10（-6）M）或AP-NTS。在髓质中，3 H-L-364，718结合的定位与L-365，031敏感的125 I-CCK-8结合相似，并且在NTS的AP和内侧而非外侧发现。在由IPN、NTS和AP制备的膜中，3 H-364，718结合具有高亲和力（Kd = 0.14 nM）、可饱和（Bmax = 20 fmol/mg蛋白质），并受到先前显示作用于胰腺CCK受体的化合物的抑制。3 H-364，718标记的受体受鸟苷酸调节，其使激动剂亲和力降低10倍而不影响拮抗剂结合。CCK受体在AP和NTS内的高密度分布和定位表明，这些受体可能在感觉传入信息的加工过程中起重要作用。
Two potent and highly selective nonpeptide antagonists, L-365,031 [1- methyl-3-(4-bromobenzoyl)amino-5-phenyl-3H-1,4 benzodiazepin-2-one] and 3H-L-364,718 [1-methyl-3-(2-indoloyl)amino-5-phenyl-3H-1,4 benzodiazepin-2-one] were used to localize “peripheral” CCK receptors in rat brain. In autoradiographic experiments, L-365,031 displaced 125I- Bolton Hunter CCK-8 binding from the interpeduncular nucleus (IPN) (IC50 = 7 X 10(-8) M), the area postrema (AP), and the nucleus tractus solitarius (NTS) without influencing specific binding to other areas, such as the cerebral cortex or the spinal tract of the trigeminal nerve. Desulfated CCK preferentially inhibited 125I-CCK binding to cerebral cortex (IC50 = 7 X 10(-8) M) rather than IPN (IC50 greater than 1 X 10(-6) M) or AP-NTS. In the medulla the localization of 3H-L- 364,718 binding was similar to L-365,031-sensitive 125I-CCK-8 binding and was found in the AP and medial, but not lateral, aspects of the NTS. In membranes prepared from IPN, NTS, and AP, 3H-364,718 binding was of high affinity (Kd = 0.14 nM), saturable (Bmax = 20 fmol/mg protein), and inhibited by compounds previously shown to act at pancreatic CCK receptors. The receptors labeled by 3H-364,718 were modulated by guanyl nucleotide, which reduced agonist affinity 10-fold without affecting antagonist binding. The localization and high density of CCK receptors in AP and NTS suggest that these receptors may play an important role in processing sensory afferent information.
在分散的小鼠胰腺腺泡细胞中，胆囊收缩素八肽和乙酰胆碱刺激的磷脂酰肌醇分解期间，锂诱导肌醇 1-磷酸的积累。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hokin-Neaverson,M;Sadeghian,K
通讯作者：
Sadeghian,K