4-β-佛波醇-12,13-二丁酸酯（PDBu）对烟碱型乙酰胆碱受体通道的直接作用，与蛋白激酶C激活无关。

Direct action of 4-beta-phorbol-12,13-dibutyrate (PDBu) on nicotinic acetylcholine receptor channel independent of protein kinase C activation.

作者信息

Nishizaki T, Sumikawa K

机构信息

Department of Psychobiology, University of California, Irvine 92717-4550, USA.

出版信息

Neurosci Lett. 1995 Mar 24;188(2):129-31. doi: 10.1016/0304-3940(95)11396-e.

DOI:10.1016/0304-3940(95)11396-e

PMID:7540739

Abstract

Torpedo acetylcholine receptor (AChR) has a protein kinase C (PKC) phosphorylation site, which modulates channel properties, on the alpha and delta subunit. The effect of a potent PKC activator, PDBu on AChR expressed into Xenopus oocytes was examined by whole cell voltage clamp recordings. The pretreatment with 4-beta-PDBu reversely accelerated desensitization of ACh-elicited membrane currents and the same effect was shown by co-application of 4-beta-PDBu and ACh without pre-incubation. Treatment with the inactive stereoisomer of phorbol ester, 4-alpha-PDBu also demonstrated an acceleration of desensitization. Furthermore, 4-beta-PDBu enhanced the rate of desensitization in mutant AChR deleting PKC phosphorylation sites on the alpha and delta subunit. These results indicate that phorbol ester directly acts on the AChR channel independent of PKC activation.

摘要

电鳐乙酰胆碱受体（AChR）在α和δ亚基上有一个蛋白激酶C（PKC）磷酸化位点，该位点可调节通道特性。通过全细胞电压钳记录，研究了一种有效的PKC激活剂佛波醇-12,13-二丁酯（PDBu）对非洲爪蟾卵母细胞中表达的AChR的影响。用4-β-PDBu预处理可反向加速ACh诱导的膜电流脱敏，且在未预孵育的情况下，将4-β-PDBu与ACh共同应用也显示出相同的效果。用佛波酯的无活性立体异构体4-α-PDBu处理也证明脱敏加速。此外，4-β-PDBu提高了缺失α和δ亚基上PKC磷酸化位点的突变型AChR的脱敏速率。这些结果表明，佛波酯直接作用于AChR通道，与PKC激活无关。