Mohell N, Nedergaard J
Eur J Pharmacol. 1985 Sep 24;115(2-3):231-40. doi: 10.1016/0014-2999(85)90695-8.
In order to investigate the coupling mechanism of alpha 1-adrenoceptors in brown adipose tissue, the effects of guanine nucleotides and cations on agonist binding were studied with a membrane fraction obtained from hamsters. The affinity of the alpha 1-receptor for the adrenergic agent was followed in competition experiments with [3H]prazosin. It was found that the addition of GTP diminished the affinity of the alpha 1-receptor for norepinephrine but not for the alpha-antagonist phentolamine. This effect seemed to be dependent upon the presence of Mg2+ and could not be observed in isolated cells, indicating an intracellular site of action. A reduction of the Mg2+ concentration from the conventional 10 mM to the more physiological level of 1 mM markedly increased the affinity of the receptor for norepinephrine; this effect again was agonist-specific. The addition of Na+ (150 mM) decreased the agonist affinity of the receptor. It is suggested that the (not adenylate cyclase-coupled) alpha 1-adrenergic pathway in brown adipose tissue also is regulated by guanine nucleotides and modulated by the cations Mg2+ and Na+, indicating an involvement of a guanine nucleotide binding protein. Such a system may therefore be a general mechanism for the transduction of hormone stimulation over the cell membrane.
为了研究棕色脂肪组织中α1 - 肾上腺素能受体的偶联机制，利用从仓鼠获得的膜组分研究了鸟嘌呤核苷酸和阳离子对激动剂结合的影响。在与[3H]哌唑嗪的竞争实验中，追踪α1 - 受体对肾上腺素能药物的亲和力。发现添加GTP会降低α1 - 受体对去甲肾上腺素的亲和力，但对α - 拮抗剂酚妥拉明的亲和力无影响。这种效应似乎依赖于Mg2 + 的存在，在分离的细胞中未观察到，表明作用位点在细胞内。将Mg2 + 浓度从常规的10 mM降低到更接近生理水平的1 mM，显著增加了受体对去甲肾上腺素的亲和力；这种效应同样具有激动剂特异性。添加Na +（150 mM）会降低受体的激动剂亲和力。有人提出，棕色脂肪组织中（不与腺苷酸环化酶偶联的）α1 - 肾上腺素能途径也受鸟嘌呤核苷酸调节，并受阳离子Mg2 + 和Na + 调制，表明涉及一种鸟嘌呤核苷酸结合蛋白。因此，这样一个系统可能是激素刺激通过细胞膜转导的一般机制。
