Atypical SCH23390 binding sites are present on bovine adrenal medullary membranes.
Atypical SCH23390 binding sites are present on bovine adrenal medullary membranes.
复制标题
牛肾上腺髓质膜上存在非典型 SCH23390 结合位点。
DOI：
10.1023/a:1007569518010
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发表时间：
2000
影响因子：
4.4
通讯作者：
Senogles,SE
中科院分区：
文献类型：
--
作者：
Dahmer,MK;Senogles,SE
D1选择性多巴胺受体激动剂抑制促分泌素刺激的牛肾上腺嗜铬细胞分泌儿茶酚胺。本研究报告的目的是使用放射性标记的D1-选择性多巴胺受体拮抗剂，SCH 23390，来表征负责这种效应的推定的D1样多巴胺受体。SCH 23390结合位点的表征表现出与经典D1样受体不一致的不寻常的药理学特征。与肾上腺髓质膜结合的[125 I] SCH 23390与非放射性碘-SCH 23390（Kd = 490 ± 50 nM）竞争，但不与（+）butaclamol竞争。其他经典的D1拮抗剂几乎没有，如果有的话，效果。与多巴胺受体激动剂的竞争表现出D1样多巴胺受体的效力特征的相对等级顺序，然而，Kis高于在其他组织中发现的。C1-APB和SKF 38393竞争[125 I] SCH 23390结合的Ki（分别为16和118 μM）与先前观察到的分泌抑制的IC 50（分别为9和100 μM）几乎相同。结合这些数据表明，肾上腺髓质膜含有一个新的SCH 23390结合位点参与抑制分泌的D1-选择性激动剂。
D1-selective dopamine receptor agonists inhibit secretagogue-stimulated catecholamine secretion from bovine adrenal chromaffin cells. The purpose of the studies reported here was to use the radiolabeled D1-selective dopamine receptor antagonist, SCH23390, to characterize putative D1-like dopamine receptors responsible for this effect. Characterization of SCH23390 binding sites demonstrated an unusual pharmacological profile inconsistent with classical D1-like receptors. [125I]SCH23390 bound to adrenal medullary membranes was competed for by non-radioactive iodo-SCH23390 (Kd = 490 ± 50 nM), but not by (+)butaclamol. Other classical D1 antagonists had little, if any, effect. Competition with dopamine receptor agonists demonstrated a relative rank order of potency profile characteristic of D1-like dopamine receptors, however, Kis were higher than those found in other tissues. The Kis for competition of [125I]SCH23390 binding by C1-APB and SKF38393 (16 and 118 μM, respectively) are nearly identical to the IC50s previously observed for inhibition of secretion (9 and 100 μM, respectively). Combined these data suggest that adrenal medullary membranes contain a novel SCH23390 binding site involved in the inhibition of secretion by D1-selective agonists.