Stereospecificity of the sensory irritation receptor for nonreactive chemicals illustrated by pinene enantiomers

被引:38
作者
Kasanen, JP
Pasanen, AL
Pasanen, P
Liesivuori, J
Kosma, VM
Alarie, Y
机构
[1] Univ Kuopio, Dept Environm Sci, FIN-70211 Kuopio, Finland
[2] Kuopio Reg Inst Occupat Hlth, FIN-70701 Kuopio, Finland
[3] Univ Kuopio, Dept Pathol & Forens Med, FIN-70211 Kuopio, Finland
[4] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA USA
关键词
sensory irritation; stereospecificity; enantiomers; alpha-pinene; beta-pinene; chirality;
D O I
10.1007/s002040050536
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
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 (P degrees), all pinenes are nonreactive chemicals. For nonreactive chemicals, P degrees and olive oil-gas partition (L-Oil) 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 P degrees and L-Oil 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 similar to 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-pinenethose 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 fan 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.
引用
收藏
页码:514 / 523
页数:10
相关论文
共 61 条
[51]  
SCHAPER M, 1993, AM IND HYG ASSOC J, V54, P488, DOI 10.1202/0002-8894(1993)054<0488:DOADFS>2.0.CO
[52]  
2
[53]  
SILVER WL, 1990, CHEM SENSES, V2, P297
[54]   ACUTE EFFECTS OF TURPENTINE VAPOR ON RATS AND MICE [J].
SPERLING, F ;
MARCUS, WL ;
COLLINS, C .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 1967, 10 (01) :8-&
[55]   CHROMATOGRAPHIC STUDIES OF THE ENANTIOMERIC COMPOSITION OF SOME THERAPEUTIC COMPOSITIONS APPLIED IN THE TREATMENT OF LIVER AND KIDNEY-DISEASES [J].
SYBILSKA, D ;
KOWALCZYK, J ;
ASZTEMBORSKA, M ;
OCHOCKA, RJ ;
LAMPARCZYK, H .
JOURNAL OF CHROMATOGRAPHY A, 1994, 665 (01) :67-73
[56]  
TALLARIDA RJ, 1988, PRINCIPLES GEN PHARM
[57]  
TAYLOR P, 1990, P1
[58]   COMPUTER-ASSISTED RECOGNITION AND QUANTITATION OF THE EFFECTS OF AIRBORNE CHEMICALS ACTING AT DIFFERENT AREAS OF THE RESPIRATORY-TRACT IN MICE [J].
VIJAYARAGHAVAN, R ;
SCHAPER, M ;
THOMPSON, R ;
STOCK, MF ;
BOYLSTEIN, LA ;
LUO, JE ;
ALARIE, Y .
ARCHIVES OF TOXICOLOGY, 1994, 68 (08) :490-499
[59]   CHARACTERISTIC MODIFICATIONS OF THE BREATHING PATTERN OF MICE TO EVALUATE THE EFFECTS OF AIRBORNE CHEMICALS ON THE RESPIRATORY-TRACT [J].
VIJAYARAGHAVAN, R ;
SCHAPER, M ;
THOMPSON, R ;
STOCK, MF ;
ALARIE, Y .
ARCHIVES OF TOXICOLOGY, 1993, 67 (07) :478-490
[60]   STEREOSPECIFIC ANTENNAL RESPONSE BY RED TURPENTINE BEETLE, DENDROCTONUS VALENS TO CHIRAL MONOTERPENES FROM PONDEROSA PINE RESIN [J].
WHITE, PR ;
HOBSON, KR .
JOURNAL OF CHEMICAL ECOLOGY, 1993, 19 (10) :2193-2202