Zou D J, Treherne J M, Stewart R R, Saunders N R, Nicholls J G
Department of Pharmacology, Universität Basel, Switzerland.
Proc Biol Sci. 1991 Oct 22;246(1315):77-82. doi: 10.1098/rspb.1991.0127.
The aim of these experiments has been to analyse the properties of receptors for the transmitter gamma-aminobutyric acid (GABA) in developing mammalian nervous system. Changes in responses of GABAB receptors have been measured after alterations of the chemical environment and the level of electrical activity. We have previously shown that when the central nervous system (CNS) of the new-born opossum, Monodelphis domestica, is cultured for three to five days in the presence of histidine, inhibition by baclofen, a GABAB agonist, disappears (Stewart et al. 1991). We have now investigated whether histidine acts indirectly by way of conversion to histamine. As with histidine, culture with 150 microM histamine for five days virtually abolished the inhibition by baclofen. The effects of histidine, as well as histamine, were blocked by mepyramine, a histamine H1-receptor antagonist, and by ranitidine, an H2-antagonist. Tetrodotoxin (TTX), which blocks all electrical activity, protected preparations from the action of histidine but not histamine. Our results suggest that histidine is converted to histamine, which reduces the efficacy of GABAB agonists. We conclude that, in the developing mammalian CNS, transmitter levels and electrical activity can selectively influence the properties of receptors.
这些实验的目的是分析发育中的哺乳动物神经系统中递质γ-氨基丁酸（GABA）受体的特性。在改变化学环境和电活动水平后，已对GABAB受体的反应变化进行了测量。我们之前已经表明，当新生负鼠（Monodelphis domestica）的中枢神经系统（CNS）在组氨酸存在的情况下培养三到五天时，GABAB激动剂巴氯芬的抑制作用消失（Stewart等人，1991年）。我们现在研究了组氨酸是否通过转化为组胺而间接发挥作用。与组氨酸一样，用150微摩尔组胺培养五天实际上消除了巴氯芬的抑制作用。组胺H1受体拮抗剂美吡拉敏和H2拮抗剂雷尼替丁可阻断组氨酸以及组胺的作用。阻断所有电活动的河豚毒素（TTX）可保护制剂免受组氨酸而非组胺的作用。我们的结果表明，组氨酸转化为组胺，从而降低了GABAB激动剂的效力。我们得出结论，在发育中的哺乳动物中枢神经系统中，递质水平和电活动可以选择性地影响受体的特性。
