Sárközi Sándor, Almássy János, Lukács Balázs, Dobrosi Nóra, Nagy Georgina, Jóna István
Department of Physiology, Medical and Health Science Centre, University of Debrecen, PO Box 22, Debrecen 4012, Hungary.
J Muscle Res Cell Motil. 2007;28(2-3):167-74. doi: 10.1007/s10974-007-9113-x. Epub 2007 Jul 20.
The effect of natural phenol derivatives was studied on skeletal type sarcoplasmic reticulum Ca(2+)-ATPase and ryanodine receptor. The majority of the tested derivatives exerted inhibitory effect on the Ca(2+)-ATPase with an ascending sequence in regard to their effectiveness (IC(50)): cineole (3.33 mM) < ortho-vanillin (IC(50 )=1.13 mM) < 4-methyl-2-nitrophenol (1104 microM) < vanillin (525 microM) < thymol (224 microM) < carvacrol (162 microM). In two cases biphasic characteristic was observed: trans-anethole and meta-anisaldehyde first caused activation followed by inhibition (with IC(50)-s of 141 and 1903 microM respectively) as their concentration was increased. In some cases (cineole, ortho-vanillin, meta-anisaldehyde) total inhibition of Ca(2+)-ATPase could not be reached as the result of the limited solubility of these drugs. Para-anisaldehyde and 6-amino-meta-cresol did not show any effect up to 3 mM. In Ca(2+) release experiments drugs were applied on heavy sarcoplasmic reticulum vesicles isolated from skeletal muscle and actively loaded with calcium. Only thymol and carvacrol were able to evoke Ca(2+) release with EC(50) values of 158 +/- 16 and 211 +/- 55 microM respectively. Furthermore the effect of thymol and carvacrol was tested on the isolated ryanodine receptor incorporated into artificial lipid bilayer. Both drugs activated the RyR when applied in concentrations identical to their EC(50) values. These observations show that small differences in the structure of phenol derivatives sometimes have little impact on their effect on the sarcoplasmic reticulum Ca(2+)-ATPase or ryanodine receptor (thymol and carvacrol) whereas in certain cases they can completely abolish a particular effect (para- and meta-anisaldehyde).
研究了天然酚类衍生物对骨骼肌型肌浆网Ca(2+)-ATP酶和兰尼碱受体的作用。大多数受试衍生物对Ca(2+)-ATP酶具有抑制作用，其效力（IC(50)）呈升序排列：桉叶油素（3.33 mM）<邻香草醛（IC(50)=1.13 mM）<4-甲基-2-硝基苯酚（1104 microM）<香草醛（525 microM）<百里香酚（224 microM）<香芹酚（162 microM）。在两种情况下观察到双相特征：反式茴香脑和间茴香醛随着浓度增加，首先引起激活，随后抑制（IC(50)分别为141和1903 microM）。在某些情况下（桉叶油素、邻香草醛、间茴香醛），由于这些药物的溶解度有限，无法实现对Ca(2+)-ATP酶的完全抑制。对甲氧基苯甲醛和6-氨基间甲酚在3 mM以下未显示任何作用。在Ca(2+)释放实验中，将药物应用于从骨骼肌分离并主动加载钙的重肌浆网小泡。只有百里香酚和香芹酚能够引起Ca(2+)释放，EC(50)值分别为158±16和211±55 microM。此外，还测试了百里香酚和香芹酚对掺入人工脂质双层的分离兰尼碱受体的作用。当以与其EC(50)值相同的浓度应用时，两种药物均激活了兰尼碱受体。这些观察结果表明，酚类衍生物结构上的微小差异有时对其对肌浆网Ca(2+)-ATP酶或兰尼碱受体的作用影响很小（百里香酚和香芹酚），而在某些情况下，它们可以完全消除特定作用（对茴香醛和间茴香醛）。
