GUANYL NUCLEOTIDE AND DIVALENT-CATION REGULATION OF CORTICAL-S2 SEROTONIN RECEPTORS
GUANYL NUCLEOTIDE AND DIVALENT-CATION REGULATION OF CORTICAL-S2 SEROTONIN RECEPTORS
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DOI：
10.1111/j.1471-4159.1984.tb05375.x
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发表时间：
1984-01-01
影响因子：
4.7
通讯作者：
TITELER, M
中科院分区：
文献类型：
--
作者：
BATTAGLIA, G;SHANNON, M;TITELER, M
计算机辅助定量分析放射配体与大鼠皮质S2血清素[5-羟色胺]受体的结合表明，同一受体群体存在两种亲和力状态。[3H]酮色林标记位点的单相拮抗剂竞争曲线表明，对拮抗剂具有1种亲和力状态的受体群体是均匀的。激动剂的双相竞争曲线表明，激动剂区分高和低激动剂亲和形式的S2受体。不同的激动剂在高和低亲和状态下的亲和性，以及高亲和形式的表观百分比是不同的。鸟嘌呤核苷酸GTP和鸟酰-5′-亚胺二磷酸[Gpp(NH)p]以及二价阳离子调节激动剂高亲和力位点的比例，这可以通过它们改变[3H]酮色酮标记的S2受体的激动剂竞争曲线来证明。GTP和Gpp(NH)p效应似乎是激动剂特异性的，因为它们不影响拮抗剂对[3H]酮色胺标记的S2受体的竞争，也不影响[3H]酮色胺与S2受体的结合。ATP和ADP对S2 - 5 -羟色胺受体的结合特性影响很小或没有影响，而GDP的作用不如GTP。这些特异性核苷酸效应的存在是第一个表明鸟嘌呤核苷酸结合蛋白参与激动剂与S2 5 -羟色胺受体相互作用机制的证据。[3H]酮色素标记的S2 - 5 -羟色胺受体的结合特性与腺苷酸环化酶偶联受体如。β。-肾上腺素，α。2受体和D-2多巴胺受体。S2 5 -羟色胺受体可能通过GTP结合蛋白与腺苷酸环化酶活性偶联。
Computer-assisted quantitative analysis of radioligand binding to rat cortical S2 serotonin [5-hydroxytryptamine] receptors indicates the existence of 2 affinity states of the same receptor population. Monophasic antagonist competition curves for [3H]ketanserin-labeled sites suggest a uniform population of receptors with 1 affinity state for antagonists. Biphasic competition curves of agonists suggest that agonists discriminate high- and low-agonist-affinity forms of the S2 receptors. The affinities of agonists for the high- and low-affinity states, and the apparent percentages of high agonist-affinity forms varies with different agonists. The guanine nucleotides GTP and guanylyl-5''-imido-diphosphate [Gpp(NH)p], as well as divalent cations, modulate the proportion of the sites with high affinity for agonists as evidenced by their ability to shift the agonist competition curves for [3H]ketanserin-labeled S2 receptors. GTP and Gpp(NH)p effects appear to be agonist-specific, as they do not affect antagonist competition for [3H]ketanserin-labeled S2 receptors, or [3H]ketanserin binding to S2 receptors. ATP and ADP have little or no effect on the binding properties of S2 serotonin receptors, whereas GDP is less potent than GTP. The presence of these specific nucleotide effects are the first evidence suggesting involvement of a guanine nucleotide-binding protein in the mechanism of agonist interaction with the S2 serotonin receptor. The binding properties of [3H]ketanserin-labeled S2 serotonin receptors strongly resemble those of adenylate-cyclase coupled receptors such as the .beta.-adrenergic, the .alpha.2-receptor, and the D-2 dopamine receptor. The S2 serotonin receptor may be coupled to adenylate cyclase activity, through a GTP binding protein.