Caratsch C G, Knoflach F, Grassi F, Eusebi F
Department of Pharmacology, University of Zurich, Switzerland.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jul;340(1):82-6. doi: 10.1007/BF00169211.
(1) The effect of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a specific activator of the protein kinase C (PrkC), on the function of junctional nicotinic acetylcholine receptors (nAChR) was examined on muscle fibres isolated from the M. flexor digitorum brevis of the rat. (2) In the presence of TPA the sensitivity of the whole endplates to iontophoretically applied ACh exhibited multiphasic oscillations: an early decrease followed by a delayed increase and, at the end again, a decrease to below pretreatment levels. This effect was more pronounced as the TPA concentration was increased in the range of 0.1-1 microM and was blocked by the PrkC-inhibitor 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine (H-7). (3) TPA (0.1-0.5 microM) shortly applied to patch-clamped fibres caused a slight decrease in nAChR-channel slope conductance without affecting the mean lifetime. In a patch the opening frequency increased over time, after an initial decrease. (4) It is concluded that specific activation of the PrkC may be of regulatory significance on nAChR function.
(1) 佛波酯12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）是蛋白激酶C（PrkC）的一种特异性激活剂，本研究检测了其对从大鼠趾短屈肌分离的肌纤维上的接头型烟碱型乙酰胆碱受体（nAChR）功能的影响。(2) 在TPA存在的情况下，终板对离子电泳施加的乙酰胆碱（ACh）的敏感性呈现多相振荡：早期下降，随后延迟上升，最后又降至预处理水平以下。在0.1 - 1微摩尔范围内，随着TPA浓度增加，这种效应更明显，并且被PrkC抑制剂1 -（5 - 异喹啉磺酰基）- 2 - 甲基哌嗪（H - 7）阻断。(3) 短暂施加于膜片钳记录的肌纤维上的TPA（0.1 - 0.5微摩尔）导致nAChR通道斜率电导略有下降，而不影响平均寿命。在一个膜片中，初始下降后，开放频率随时间增加。(4) 得出的结论是，PrkC的特异性激活可能对nAChR功能具有调节意义。
