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首页> 外文期刊>Archives of Toxicology >Stereospecificity of the sensory irritation receptor for nonreactive chemicals illustrated by pinene enantiomers.
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Stereospecificity of the sensory irritation receptor for nonreactive chemicals illustrated by pinene enantiomers.

机译：pin烯对映体对非反应性化学物质的感觉刺激受体的立体特异性。

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To clarify the existence of a receptor protein for sensory irritants in trigeminal nerve endings, D- [i.e. (+)] and L- [i.e. (-)] enantiomers of alpha- and beta-pinene as models of nonreactive chemicals were evaluated for their potency in outbred OF1 and NIH/S mice using ASTM E981-84 bioassay. All pinenes possess sensory irritation properties and also induced sedation and signs of anaesthesia but had no pulmonary irritation effects. According to the ratio of RD50 (i.e. concentration which causes a 50% decrease in respiratory rate,f) and vapour pressure (Po), all pinenes are nonreactive chemicals. For nonreactive chemicals, Po and olive oil-gas partition (Loil) can be used to estimate their potency as sensory irritant. Thus, for enantiomers with identical physicochemical properties, the estimated RD50 values are the same. In addition, although alpha- and beta-pinene do not have identical Po and Loil values, their estimated potencies are quite close. However, the experimental results showed that D-enantiomers of pinenes were the most potent as sensory irritants and a difference in potency also exists between alpha- and beta-pinene. RD50 for D-enantiomers of alpha- and beta-pinene were almost equal, 1053 ppm and 1279 ppm in OF1 strain and 1107 ppm and 1419 ppm in NIH/S strain, respectively. Values differed by a factor of approximately 4 to 5 from L-beta-pinene for which the RD50 was 4663 ppm in OF1 and 5811 ppm in NIH/S mice. RD50 could not be determined for L-alpha-pinene; this pinene was almost inactive. D-alpha-pinene seems to best fit the receptor because its experimental RD50 was one-half of the estimated value while for D-beta-pinene those values were equal. On the contrary, L-beta-pinene was about 3 to 4 times less potent than estimated. L-alpha-pinene was only slightly active although it was estimated to be as potent as D-alpha-pinene. The remarkable difference in potency between L-enantiometers is most likely due to a structural difference between alpha- and beta-pinene: the more flexible beta-pinene can bend to fit into the receptor better than the rigid alpha-pinene. The results showed that the commonly used physicochemical descriptors cannot fully explain the potency of these chemicals; their three-dimensional structure should also be considered. Because of the stereospecificity of pinenes, a target site for nonreactive sensory irritants is most likely a receptor protein containing a chiral lipophilic pocket.
机译：为了阐明三叉神经末梢感觉刺激性受体蛋白的存在，D- [即（+）]和L- [即（-）]使用ASTM E981-84生物测定法评估了作为非反应性化学物质模型的α-和β-pine烯的对映体在异种OF1和NIH / S小鼠中的效力。所有松子都具有感觉刺激性，并具有镇静作用和麻醉的征象，但没有肺刺激作用。根据RD50（即引起呼吸频率f降低50％的浓度）和蒸气压（Po）的比率，所有松油均为非反应性化学物质。对于非反应性化学品，可以使用Po和橄榄油气分配器（Loil）来评估其作为感觉刺激性的效力。因此，对于具有相同物理化学性质的对映异构体，估计的RD50值相同。此外，尽管α-pine烯和β-pine烯的Po和Loil值不同，但它们的估计效价非常接近。然而，实验结果表明，松树酮的D-对映异构体是最有效的感觉刺激物，α-和β-pine烯之间的效力也存在差异。 α-和β-pine烯的D对映体的RD50几乎相等，在OF1菌株中分别为1053 ppm和1279 ppm，在NIH / S菌株中分别为1107 ppm和1419 ppm。与L-β-pine烯的值相差约4到5，L-β-pine烯的RD50在OF1中为4663 ppm，在NIH / S小鼠中为5811 ppm。无法确定L-α-not烯的RD50。 pin烯几乎没有活性。 D-α-pine烯似乎最适合该受体，因为其实验RD50为估计值的一半，而D-β-pine烯的这些值相等。相反，L-β-pine烯的效力比估计值低约3至4倍。 L-α-pine烯仅略有活性，尽管据估计与D-α-pine烯一样有效。 L-对映异构体之间效价的显着差异很可能是由于α-beta烯与β-pine烯之间的结构差异：与刚性α-pine烯相比，更具柔韧性的β-pine烯可以弯曲以更好地适合受体。结果表明，常用的理化指标不能完全解释这些化学药品的效力。还应考虑它们的三维结构。由于松果的立体特异性，非反应性感觉刺激物的靶位点很可能是含有手性亲脂性口袋的受体蛋白。

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