Differential regulation of the α2-adrenergic receptor by Na+ and guanine nucleotides
Differential regulation of the α2-adrenergic receptor by Na+ and guanine nucleotides
复制标题
Na+ 和鸟嘌呤核苷酸对 α2-肾上腺素能受体的差异调节
DOI：
10.1038/288709a0
复制
发表时间：
1980
期刊：
影响因子：
64.8
通讯作者：
R. Lefkowitz
中科院分区：
文献类型：
--
作者：
T. Michel;B. Hoffman;R. Lefkowitz
Many hormones interact with receptors which stimulate the enzyme adenylate cyclase. Less well characterized are those receptors which mediate an inhibition of adenylate cyclase activity1. However, guanine nucleotides are clearly important in the regulation of both stimulatory and inhibitory receptors2. Monovalent cations, notably Na+, regulate many inhibitory receptor systems but apparently not stimulatory receptors1. We investigate here the effects of Na+ and guanine nucleotides on the adenylate cyclase-coupled inhibitory α2-adrenergic receptor of the rabbit platelet3. Computer modelling of adrenaline competition curves with 3H-dihydroergocryptine (3H-DHE) indicates that adrenaline induces two distinct affinity states of the α2 receptor—one of higher (α2H) and the other of lower (α2L) affinity. Guanyl-5′-yl-imidodiphosphate (Gpp(NH)p) seems to reduce adrenaline affinity by converting the high-affinity state into the low-affinity form of the receptor. In contrast, Na+ reduces adrenaline affinity at both the high- and low-affinity states of the α2 receptor while preserving receptor heterogeneity. Thus, guanine nucleotides and Na+ differ in the manner by which each reduces agonist affinity for the α2-adrenergic receptor.
