Clark M A, Korte A, Egan R W
Schering Plough Research Institute, Kenilworth, NJ 07033.
Agents Actions. 1993 Nov;40(3-4):129-34. doi: 10.1007/BF01984051.
Agonist occupancy of high affinity histamine H3 receptors on AtT-20 cells induces increased ACTH release. However, the signal transduction process by which this occurs is presently unknown. As a first step in characterizing this pathway, we have examined the effects of a variety of nucleotides and nucleotide analogs on Na-methylhistamine binding to these receptors. Nonhydrolyzable guanine nucleotide analogs inhibit up to 40% of the [3H]Na-methylhistamine binding by increasing the dissociation rate of the ligand from the receptor and, thereby, reducing receptor affinity. Pertussis toxin also decreases the affinity of the H3 receptors and ADP ribosylates a 41 kDa protein. Neither GTP gamma S nor pertussis toxin change Bmax. These data indicate that the H3 receptors on these cells are coupled to a G protein of the Gi subclass.
激动剂占据AtT - 20细胞上的高亲和力组胺H3受体可诱导促肾上腺皮质激素（ACTH）释放增加。然而，目前尚不清楚其发生的信号转导过程。作为表征该途径的第一步，我们研究了多种核苷酸和核苷酸类似物对[3H] - N - 甲基组胺与这些受体结合的影响。不可水解的鸟嘌呤核苷酸类似物通过增加配体从受体的解离速率，从而降低受体亲和力，抑制高达40%的[3H] - N - 甲基组胺结合。百日咳毒素也会降低H3受体的亲和力，并使一种41 kDa的蛋白质发生ADP核糖基化。GTPγS和百日咳毒素均不改变最大结合容量（Bmax）。这些数据表明，这些细胞上的H3受体与Gi亚类的G蛋白偶联。
