Depth-dependent change in membrane fluidity by phenolic compounds in bovine platelets and its relationship with their effects on aggregation and adenylate cyclase activity.
The effects of phenolic compounds on membrane fluidity of bovine blood platelets were investigated by studies on the fluorescence anisotropies of diphenylhexatriene (DPH) and its ionic derivatives to clarify the relationship of these effects with the inhibitory effects of the compounds on aggregation. Among the phenolic compounds tested, monohydric phenols (phenol and two monosubstituted derivatives) decreased the fluorescence anisotropy of DPH, which is thought to be located within the hydrophobic core of the membrane, in concentration ranges in which they inhibited platelet aggregation. On the other hand, they had little or no effects on the fluorescence anisotropies of the ionic derivatives of DPH, which are thought to be located in the interfacial region of the lipid bilayer. Consistent with their effects on the fluorescence anisotropy of DPH, these monohydric phenols increased the intracellular cAMP concentration. Thus, these monohydric phenols may inhibit platelet function by stimulation of adenylate cyclase mediated by perturbation of the central region of the membrane lipid bilayer. On the other hand, pyrocatechol and pyrogallol, which have two and three phenolic hydroxyl groups and have much larger electron donor activities than the monohydric phenols tested, inhibited platelet function by a different mechanism, because they did not cause increase in either membrane fluidity or the cAMP concentration of platelets.
Kitagawa
S
S
Niigata College of Pharmacy, Japan.
Orinaka
M
M
Hirata
H
H
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002417:Cattle; D000242:Cyclic AMP / Q000032:analysis; D004161:Diphenylhexatriene / Q000031:analogs & derivatives; D005454:Fluorescence Polarization; D005456:Fluorescent Dyes; D008560:Membrane Fluidity / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*
D005456:Fluorescent Dyes; D010636:Phenols; D010975:Platelet Aggregation Inhibitors; D004161:Diphenylhexatriene; C033628:1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene; C037385:1-(4'-carboxyethyl)-6-diphenyl-1,3,5-hexatriene; D000242:Cyclic AMP