Sugden D, Klein D C
J Biol Chem. 1987 Jun 5;262(16):7447-50.
The adrenergic regulation of cyclic GMP in isolated pinealocytes was investigated. In this cell, norepinephrine stimulates cyclic GMP and cyclic AMP greater than 100-fold by activating both alpha 1- and beta-adrenoceptors. beta-Adrenergic activation is a requisite event and is potentiated by alpha 1-adrenergic activation (Vanecek, J., Sugden, D., Weller, J. L., and Klein, D. C. (1985) Endocrinology 116, 2167-2173). The current study found that cholera toxin could substitute for beta-adrenergic agonists in stimulating pinealocyte cyclic GMP content, as has been found to be the case for cyclic AMP. Treatment with cholera toxin alone (1 microgram/ml for 90 min) had a small effect (2- to 4-fold increase) on cyclic GMP; addition of the alpha 1-adrenergic agonists, phenylephrine, cirazoline, or methoxamine to cholera toxin-treated cells rapidly (peak at 5 min) caused a further 30- to 300-fold increase. The alpha 1-adrenergic agonists had little effect by themselves at concentrations which potentiated the effects of cholera toxin. The potentiating effect of phenylephrine was inhibited nearly completely by an alpha 1-adrenergic antagonist, but not by either an alpha 2- or beta-adrenergic antagonist. The purified cholera toxin subunits A and B did not stimulate cyclic GMP either alone or in the presence of phenylephrine. Furthermore, the potentiating action of phenylephrine was observed following 90 min but not 20 min of cholera toxin pretreatment. these results suggest that the regulation of cyclic GMP levels in the pineal gland involves an Ns-like GTP-binding regulatory protein. This is of interest because it is the first indication that cyclic GMP is regulated by such a GTP-binding protein in nonretinal tissue. It remains to be determined whether the mechanisms involved in the transmembrane regulation of cyclic AMP and cyclic GMP in any other tissue are similar.
研究了分离的松果体细胞中环磷酸鸟苷（cGMP）的肾上腺素能调节。在这种细胞中，去甲肾上腺素通过激活α1和β肾上腺素能受体，刺激cGMP和环磷酸腺苷（cAMP）增加超过100倍。β肾上腺素能激活是一个必要事件，并被α1肾上腺素能激活所增强（瓦内塞克，J.，萨格登，D.，韦勒，J.L.，和克莱因，D.C.（1985年）《内分泌学》116，2167 - 2173）。当前研究发现，霍乱毒素可以替代β肾上腺素能激动剂来刺激松果体细胞的cGMP含量，正如在cAMP的情况中所发现的那样。单独用霍乱毒素处理（1微克/毫升，处理90分钟）对cGMP有较小影响（增加2至4倍）；向经霍乱毒素处理的细胞中添加α1肾上腺素能激动剂去氧肾上腺素、可乐定或甲氧明会迅速（在5分钟时达到峰值）导致进一步增加30至300倍。α1肾上腺素能激动剂在增强霍乱毒素作用的浓度下单独作用时影响很小。去氧肾上腺素的增强作用几乎完全被α1肾上腺素能拮抗剂抑制，但不被α2或β肾上腺素能拮抗剂抑制。纯化的霍乱毒素亚基A和B单独或在去氧肾上腺素存在时都不刺激cGMP。此外，在霍乱毒素预处理90分钟后观察到了去氧肾上腺素的增强作用，但预处理20分钟时未观察到。这些结果表明，松果体中cGMP水平的调节涉及一种类似Ns的鸟苷三磷酸（GTP）结合调节蛋白。这很有意思，因为这是首次表明在非视网膜组织中cGMP受这种GTP结合蛋白调节。其他任何组织中环磷酸腺苷和环磷酸鸟苷跨膜调节所涉及的机制是否相似还有待确定。
