卡巴胆碱-佛波酯在毒蕈碱受体处的相互作用调节兔纹状体切片中多巴胺的释放。

Carbachol-phorbol ester interactions at muscarinic receptors modulating dopamine release from rabbit striatal slices.

作者信息

Cubeddu L X, Hoffmann I S, Talmaciu R K, Diliberto P, Lovemberg T

机构信息

Department of Pharmacology, School of Pharmacy, Central University of Venezuela, Caracas.

出版信息

Neurosci Lett. 1991 Oct 14;131(2):245-8. doi: 10.1016/0304-3940(91)90624-3.

DOI:10.1016/0304-3940(91)90624-3

PMID:1762698

Abstract

Both 4-beta-12,13-dibutyrate phorbol-ester (PDBu) (EC50% = 82 +/- 12 nM) and carbachol (EC50% = 2.3 +/- 0.3.5 microM) enhanced dopamine (DA) release from rabbit striatal slices. No additivity was observed when slices were treated simultaneously with 0.1 microM PDBu and 10 microM carbachol. Pretreatment with PDBu (0.01-0.1 microM) abolished carbachol-induced facilitation of DA release. Pretreatment with carbachol (3-100 microM) antagonized the enhancement in DA release produced by PDBu. The effect of carbachol was blocked by atropine (0.1 microM) and not by hexamethonium (10 microM). The effect of PDBu was not modified by the acetylcholine receptor (AChR) antagonists. If muscarinic (MAChR) MAChR were blocked by atropine (0.1 microM), pretreatment with carbachol failed to antagonize PDBu-induced facilitation of DA release. This is the first report to indicate that activation of M1-MAChR by an agonist prevents the effects of an active phorbol-ester. We suggest that activation of M1-MAChR enhances DA release possibly through activation of PKC.

摘要

4-β-12,13-二丁酸佛波酯（PDBu）（半数有效浓度[EC50%] = 82±12 nM）和卡巴胆碱（EC50% = 2.3±0.35 μM）均可增强兔纹状体切片中多巴胺（DA）的释放。当切片同时用0.1 μM PDBu和10 μM卡巴胆碱处理时，未观察到相加作用。用PDBu（0.01 - 0.1 μM）预处理可消除卡巴胆碱诱导的DA释放促进作用。用卡巴胆碱（3 - 100 μM）预处理可拮抗PDBu所产生的DA释放增强作用。卡巴胆碱的作用可被阿托品（0.1 μM）阻断，而不被六甲铵（10 μM）阻断。PDBu的作用未被乙酰胆碱受体（AChR）拮抗剂改变。如果毒蕈碱型（MAChR）MAChR被阿托品（0.1 μM）阻断，用卡巴胆碱预处理则无法拮抗PDBu诱导的DA释放促进作用。这是第一份表明激动剂激活M1 - MAChR可阻止活性佛波酯作用的报告。我们认为，M1 - MAChR的激活可能通过蛋白激酶C（PKC）的激活增强DA释放。