Involvement of receptor reserve in D-1 agonistic action of (-)-stepholidine in lesioned rats
文献类型：期刊论文
| 作者 | Zou, LL; Liu, JA; Jin, GZ
|
| 刊名 | BIOCHEMICAL PHARMACOLOGY
 |
| 出版日期 | 1997-07-15 |
| 卷号 | 54期号:2页码:233-240 |
| 关键词 | (-)-stepholidine D-1 dopamine receptor partial agonist receptor reserve adenylate cyclase rotational behavior |
| ISSN号 | 0006-2952 |
| DOI | 10.1016/S0006-2952(97)00153-6 |
| 文献子类 | Article |
| 英文摘要 | (-)-Stepholidine (SPD) is a natural produce. Previous studies had demonstrated that SPD displayed D-1 agonism in unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats and D-1 antagonism in reserpinized rats and normal rats. The aim of the present study was to explain this peculiar pharmacological action based on behavioral and biochemical experiments. In the unilaterally 6-OHDA-lesioned rats, SPD (4 mg/kg, s.c.) induced contralateral rotation as did apomorphine (APO), but the rotation response to SPD was 60% lower than that to APO (0.5 mg/kg, i.p.). Coadministration with APO (0.5 mg/kg, i.p.) and SPD (0.5 to 10 mg/kg, s.c.) produced a biphasic action curve; At low doses (0.5 or 1 mg/kg), SPD potentiated APO action; at high doses (4 or 10 mg/kg), however, SPD suppressed APO. In striatal homogenate of the unilaterally lesioned rats, SPD stimulated cyclic AMP (cAMP) formation and produced a maximal response comparable to that of dopamine (DA) in the denervated striatum, but 70% lower than that of DA in the intact striatum. Coadministration of 10 mu M DA with various concentrations of SPD yielded different results, with a biphasic response in the intact side and a synergistic effect in the denervated side. Furthermore, based on the determination of receptor mediated cAMP formation, the D-1 receptor reserve was analyzed in both denervated and intact striatum by using the DA receptor inactivator N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). The results showed that following EEDQ administration, the receptor density [revealed by [H-3]R(+)-7-chloro-8-hydroxy-3-methyl 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine ([H-3]SCH-23390) binding] and the agonist-stimulated adenylate cyclase (AC) activity (revealed by cAMP formation) were reduced concur rently. In the intact striatum, the reduction in SPD-stimulated AC activity paralleled the receptor loss, indicating the absence of receptor reserve, while in the denervated striatum the reduction in AC activity was less than the receptor loss, indicating a significant level of receptor reserve (estimated 16.4%). By comparison, receptor reserve for DA was 45.7 and 25.3% in the denervated and intact striatum, respectively, representing an 80% increase of receptor reserve. In conclusion, SPD is a D-1 partial agonist, and receptor reserve permits SPD to display its D-1 agonistic action in the unilaterally 6-OHDA-lesioned rats. (C) 1997 Elsevier Science Inc. |
| WOS关键词 | TYROSINE-HYDROXYLASE ACTIVITY ; DOPAMINE RECEPTOR ; ADENYLATE-CYCLASE ; CORPUS STRIATUM ; L-STEPHOLIDINE ; TETRAHYDROPROTOBERBERINES ; ANTAGONISTS ; ANALOGS ; INVIVO ; BRAIN |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:A1997XR39600003 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/274895]  |
| 专题 | 院士及顾问专家 |
| 作者单位 | CHINESE ACAD SCI,SHANGHAI INST MAT MED,DEPT PHARMACOL,SHANGHAI 200031,PEOPLES R CHINA |
| 推荐引用方式 GB/T 7714 | Zou, LL,Liu, JA,Jin, GZ. Involvement of receptor reserve in D-1 agonistic action of (-)-stepholidine in lesioned rats[J]. BIOCHEMICAL PHARMACOLOGY,1997,54(2):233-240. |
| APA | Zou, LL,Liu, JA,&Jin, GZ.(1997).Involvement of receptor reserve in D-1 agonistic action of (-)-stepholidine in lesioned rats.BIOCHEMICAL PHARMACOLOGY,54(2),233-240. |
| MLA | Zou, LL,et al."Involvement of receptor reserve in D-1 agonistic action of (-)-stepholidine in lesioned rats".BIOCHEMICAL PHARMACOLOGY 54.2(1997):233-240. |
入库方式： OAI收割
来源：上海药物研究所
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