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新生大鼠脑中阿片受体和GTP结合调节蛋白的发育

Development of opiate receptors and GTP-binding regulatory proteins in neonatal rat brain.

作者信息

Milligan G, Streaty R A, Gierschik P, Spiegel A M, Klee W A

出版信息

J Biol Chem. 1987 Jun 25;262(18):8626-30.

PMID:3036816
Abstract

The mu and delta opiate receptors present in rat brain were measured independently during postnatal development. The numbers of delta receptors were almost undetectable at birth and increased substantially during the first few weeks, whereas the numbers of mu receptors remained relatively constant. Activation of either of these receptors caused inhibition of adenylate cyclase, but inhibition coupled to mu receptors was much smaller than that associated with delta receptors at all ages. Attempts to use pertussis toxin-catalyzed ADP-ribosylation as an assay for the GTP-binding proteins Ni and No were hampered by the development of an NADase with age. However, specific antibodies directed against the alpha subunits of Ni or No allowed separate quantitation of these transducer proteins. Both increased with age. No is present at levels at least 5-fold higher than Ni in the adult rat brain. The N proteins are in vast excess over receptors and as such are unlikely to be limiting factors in receptor function. The data further suggest that the number of opiate receptors present throughout neonatal development is in excess over that required for optimal function.

摘要

在出生后的发育过程中,对大鼠脑中的μ和δ阿片受体进行了独立测量。δ受体的数量在出生时几乎检测不到,在最初几周内大幅增加,而μ受体的数量则保持相对恒定。激活这两种受体中的任何一种都会导致腺苷酸环化酶的抑制,但与μ受体偶联的抑制作用在所有年龄段都比与δ受体相关的抑制作用小得多。由于随着年龄增长会产生一种NAD酶,因此试图使用百日咳毒素催化的ADP-核糖基化来检测GTP结合蛋白Ni和No受到了阻碍。然而,针对Ni或No的α亚基的特异性抗体允许对这些转导蛋白进行单独定量。两者都随着年龄的增长而增加。在成年大鼠脑中,No的含量至少比Ni高5倍。N蛋白的数量远远超过受体,因此不太可能是受体功能的限制因素。数据进一步表明,在整个新生儿发育过程中,阿片受体的数量超过了最佳功能所需的数量。

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