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首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Roles of Dopaminergic D1 and D2 Receptors in Catecholamine Release from the Rat Adrenal Medulla
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Roles of Dopaminergic D1 and D2 Receptors in Catecholamine Release from the Rat Adrenal Medulla

机译：多巴胺能D1和D2受体在大鼠肾上腺髓质释放儿茶酚胺中的作用

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摘要

The aim of the present study was designed to establish comparatively the inhibitory effects of D1-like and D2-like dopaminergic receptor agonists, SKF81297 and R(-)-TNPA on the release of catecholamines (CA) evoked by cholinergic stimulation and membrane depolarization from the isolated perfused model of the rat adrenal medulla. SKF81297 (30μM) and R-(-)-TNPA (30μM) perfused into an adrenal vein for 60 min, produced great inhibition in the CA secretory responses evoked by ACh (5.32×10- 3 M), DMPP (10-4 M), McN-A-343 (10-4 M), high K+ (5.6×10-2 M), Bay-K-8644 (10μM), and cyclopiazonic acid (10μM), respectively. For the release of CA evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: SKF81297>R-(-)-TNPA. However, R(+)-SCH23390, a selectve D1-like dopaminergic receptor antagonist, and S(-)-raclopride, a selectve D2-like dopaminergic receptor antagonist, enhanced the CA secretory responses evoked by ACh, high K+, DMPP, McN-A-343, Bay-K-8644 and cyclopiazonic acid only for 0~4 min. The rank order for the enhancement of CA release evoked by high K+, McN-A-343 and cyclopiazonic acid was R(+)-SCH23390>S(-)-raclopride. Also, the rank order for ACh, DMPP and Bay-K-8644 was S(-)-raclopride > R(+)-SCH23390. Taken together, these results demonstrate that both SKF81297 and R-(-)-TNPA inhibit the CA release evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors and the membrane depolarization from the isolated perfused rat adrenal gland without affecting the basal release, respectively, but both R(+)-SCH23390 and S(-)-raclopride facilitate the CA release evoked by them. It seems likely that the inhibitory effects of SKF81297 and R-(-)-TNPA are mediated by the activation of D1-like and D2-like dopaminergic receptors located on the rat adrenomedullary chromaffin cells, respectively, whereas the facilitatory effects of R(+)-SCH23390 and S(-)-raclopride are mediated by the blockade of D1-like and D2-like dopaminergic receptors, respectively: this action is possibly associated with extra- and intracellular calcium mobilization. Based on these results, it is thought that the presence of dopaminergic D1 receptors may play an important role in regulation of the rat adrenomedullary CA secretion, in addition to well-known dopaminergic D2 receptors.
机译：本研究的目的旨在比较确定D 1 -样和D 2 -样多巴胺能受体激动剂SKF81297和R（-）-TNPA的抑制作用分离的大鼠肾上腺髓质灌注模型中胆碱能刺激和膜去极化引起的儿茶酚胺（CA）释放。 SKF81297（30μM）和R-（-）-TNPA（30μM）注入肾上腺静脉60分钟，对ACh引起的CA分泌反应产生极大的抑制作用（5.32×10 -3 M） ，DMPP（10 -4 M），McN-A-343（10 -4 M），高K + （5.6×10 < sup> -2 M），Bay-K-8644（10μM）和环吡唑酸（10μM）。对于ACh，高K + ，DMPP，McN-A-343，Bay-K-8644和环吡嗪酸引起的CA释放，获得了以下抑制效力等级：SKF81297> R -（-）-TNPA。然而，选择性的D 1 样多巴胺能受体拮抗剂R（+）-SCH23390和选择性的D 2 样多巴胺能受体拮抗剂S（-）-雷氯必利。 ，仅在0〜4分钟内增强了ACh，高K + ，DMPP，McN-A-343，Bay-K-8644和环吡嗪酸引起的CA分泌反应。高K + ，McN-A-343和环吡嗪酸引起的CA释放增强的顺序为R（+）-SCH23390> S（-）-雷氯必利。另外，ACh，DMPP和Bay-K-8644的等级顺序为S（-）-雷氯必利> R（+）-SCH23390。综上所述，这些结果表明，SKF81297和R-（-）-TNPA均能抑制胆碱能（烟碱和毒蕈碱）受体的刺激引起的CA释放以及分离的灌注大鼠肾上腺的膜去极化作用，而不会影响基础释放，分别，但R（+）-SCH23390和S（-）-雷氯必利均能促进它们引起的CA释放。 SKF81297和R-（-）-TNPA的抑制作用似乎可能是由位于其上的D 1 样和D 2 样多巴胺能受体的激活介导的。大鼠肾上腺髓质嗜铬细胞，而R（+）-SCH23390和S（-）-雷氯必利的促进作用是通过阻断D 1 样和D 2 < -sub-样多巴胺能受体：这种作用可能与细胞外和细胞内钙动员有关。根据这些结果，认为多巴胺能D 1 受体的存在，除了众所周知的多巴胺能D 2 <，可能在调节大鼠肾上腺髓质CA的分泌中起重要作用。 / sub>受体。

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