ESR ANALYSIS WITH LONG-CHAIN ALKYL SPIN LABELS IN BOVINE BLOOD-PLATELETS - RELATIONSHIP BETWEEN THE INCREASE IN MEMBRANE FLUIDITY BY ALCOHOLS AND PHENOLIC-COMPOUNDS AND THEIR INHIBITORY EFFECTS ON AGGREGATION

被引:41
作者
KITAGAWA, S [1 ]
KAMETANI, F [1 ]
TSUCHIYA, K [1 ]
SAKURAI, H [1 ]
机构
[1] UNIV TOKUSHIMA,FAC PHARMACEUT SCI,ANALYT CHEM LAB,TOKUSHIMA 770,JAPAN
关键词
(Bovine platelet); Alcohol; ESR; Membrane fluidity; Phenol; Platelet aggregation; Spin label;
D O I
10.1016/0005-2736(90)90075-Y
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Four spin-labeled probes (5-doxylstearic acid (5-NS), its methyl ester (5-NMS), 16-doxylmethylstearate (16-NMS) and 4-(N,N-dimethyl-N-pentadecy)ammonium-2,2,6,6-tetramethylpiperidine-1-oxyl (CAT-15)) were used to monitor membrane fluidity change in bovine platelets induced by three alkyl alcohols, benzyl alcohol and two phenolic compounds. The relationship between the increase in membrane fluidity induced by these compounds and their inhibitory effects on platelet aggregation was observed. Experiments with the four probes showed that n-hexyl alcohol induced decreases in the order parameter of 5-NS and apparent rotational correlation times of the other probes at the same minimal alcohol concentration. The decreases were observed in the concentration range that inhibited aggregation. n-Amyl alcohol and n-butyl alcohol decreased the values of the parameters of the above mentioned only at higher concentrations that were dependent on their hydrophobicities. Like alkyl alcohols, benzyl alcohol and phenolic compounds decreased the values of the parameters in the concentration ranges in which these compounds inhibited platelet aggregation. The concentration of these compounds causing 50% inhibition of platelet aggregation, the IC50 values, and data on 5-NS-labeled platelets indicated that they inhibited aggregation and decreased the value of the order parameter at lower concentrations relative to their Poct values in comparison to the effective concentrations of alcohols. Phenolic compounds also decreased the values of the apparent rotational correlation times of 5-NMS and 16-NMS. These results indicate that the inhibition of platelet aggregation by alcohols and phenolic compounds is due to membrane perturbation in wide range in depths within the lipid bilayer. © 1990.
引用
收藏
页码:123 / 129
页数:7
相关论文
共 34 条
[1]   EFFECTS OF OXYGEN ON THE METABOLISM OF NITROXIDE SPIN LABELS IN CELLS [J].
CHEN, K ;
GLOCKNER, JF ;
MORSE, PD ;
SWARTZ, HM .
BIOCHEMISTRY, 1989, 28 (06) :2496-2501
[2]  
CHIN JH, 1981, MOL PHARMACOL, V19, P425
[3]   BENZYL ALCOHOL INCREASES MEMBRANE FLUIDITY AND MODULATES CYCLIC-AMP SYNTHESIS IN INTACT RENAL EPITHELIAL-CELLS [J].
FRIEDLANDER, G ;
LEGRIMELLEC, C ;
GIOCONDI, MC ;
AMIEL, C .
BIOCHIMICA ET BIOPHYSICA ACTA, 1987, 903 (02) :341-348
[4]   STRUCTURE-ACTIVITY-RELATIONSHIPS OF 4'-O-SUBSTITUTED 1-BENZYLISOQUINOLINES WITH RESPECT TO THEIR ACTIONS ON THE CELL-MEMBRANE OF BLOOD-PLATELETS AND ERYTHROCYTES [J].
FUJII, T ;
SATO, T ;
TAMURA, A ;
KOMETANI, M ;
NAKAO, K ;
FUJITANI, K ;
KODAMA, K ;
AKASU, M .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 146 (2-3) :285-290
[5]   PARAMAGNETIC-RESONANCE SPECTRA OF SPIN LABELS IN PHOSPHOLIPID MEMBRANES [J].
GAFFNEY, BJ ;
MCCONNELL, HM .
JOURNAL OF MAGNETIC RESONANCE, 1974, 16 (01) :1-28
[6]  
GORDON LM, 1980, J BIOL CHEM, V255, P4519
[7]   THERMOTROPIC LIPID PHASE SEPARATIONS IN HUMAN-PLATELET AND RAT-LIVER PLASMA-MEMBRANES [J].
GORDON, LM ;
MOBLEY, PW ;
ESGATE, JA ;
HOFMANN, G ;
WHETTON, AD ;
HOUSLAY, MD .
JOURNAL OF MEMBRANE BIOLOGY, 1983, 76 (02) :139-149
[8]  
Hansch C., 1979, SUBSTITUENT CONSTANT
[9]   SPIN LABEL STUDY OF THE EFFECT OF TICLOPIDINE ON PLATELETS [J].
HONGO, T ;
SETAKA, M ;
KWAN, T .
JAPANESE JOURNAL OF PHARMACOLOGY, 1985, 39 (01) :59-66
[10]  
HUBBELL WL, 1971, J AM CHEM SOC, V93, P314