Effects of alcohols on fluorescence anisotropies of diphenylhexatriene and its derivatives in bovine blood platelets: relationships of the depth-dependent change in membrane fluidity by alcohols with their effects on platelet aggregation and adenylate cyclase activity.
The effects of three short-chain alkyl alcohols and benzyl alcohol on the membrane fluidity of bovine blood platelets were investigated by studies on the fluorescence anisotropies of diphenylhexatriene (DPH), its cationic trimethylammonium derivative (TMA-DPH) and its anionic propionic acid derivative (DPH-PA). These alcohols decreased the fluorescence anisotropy of DPH, which is thought to be located within the hydrophobic core of the membrane, in concentration ranges that inhibited platelet aggregation. On the other hand, they had little or no effects on the fluorescence anisotropy of DPH-PA which is thought to be located in the interfacial region of the lipid bilayer. Likewise, they had little or no effects on the fluorescence anisotropy of TMA-DPH, which is also thought to be located in the interfacial region of the lipid bilayer, either when the probe was located in the outer layer of the plasma membrane or when the probe was located in the inner membrane compartment. These results suggest that alcohols mainly increase the fluidity in the central region of the lipid bilayer. Consistent with their effects on the fluorescence anisotropy of DPH, these alcohols increased the intracellular cyclic AMP concentration. Thus alcohols may inhibit platelet function due to stimulation of adenylate cyclase, which is mediated by perturbation of the central region of the membrane lipid bilayer.
Kitagawa
S
S
Niigata College of Pharmacy, Niigata, Japan.
Hirata
H
H
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D004161:Diphenylhexatriene / Q000737:chemistry*; D005454:Fluorescence Polarization; D008051:Lipid Bilayers; D008560:Membrane Fluidity / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors
D000438:Alcohols; D008051:Lipid Bilayers; D010975:Platelet Aggregation Inhibitors; D004161:Diphenylhexatriene; D000242:Cyclic AMP; D000262:Adenylyl Cyclases