Prostaglandin release by aliphatic alcohols from the rat isolated lung.
1. A comparative study has been made of the abilities of members of a homologous series of aliphatic alcohols to release prostaglandins from the rat isolated perfused lung. 2. Infusions of low concentrations (0.002 mmol--0.2 mmol) of methyl, ethyl, n-propyl, i-propyl, n-butyl and t-butyl alcohol for periods of up to 5 min was accompanied by the continuous output of prostaglandins into the venous effluent, as measured by biological assay. Maximal release occurred with methyl and ethyl alcohols, the releasing abilities of the rest being in the order of n-propyl> i-propyl> n-butyl> >t-butyl. Radiomimmunoassay revealed that both PGE2 and PGF2 alpha were released by ethyl alcohol with the former being in up to 10 times greater quantities than the latter. However, the amounts of these prostaglandins failed to account for the total release of active substances as measured by bioassay. 3. Examination of concentration-response relationship showed that as the concentration of methyl, ethyl and n-propyl alcohol was increased prostaglandin output also increased, but that after reaching a maximum further increase in alcohol concentration resulted in diminished release. In contrast, the lowest concentration of i-propyl, n-butyl and t-butyl alcohol utilized (0.002 mmol) caused highest prostaglandin output and release declined as the concentration was increased. Release by ethyl alcohol (0.02 mmol) was inhibited by t-butyl alcohol (0.2 mmol). 4. Thus aliphatic alcohols can not only release prostaglandins but also depress release. Both properties appear to be possessed by each member of the series, their relative prominence varying in each compound. Release is the predominant action of the low molecular weight, short chain compounds whereas depression of release is the most prominent property of those of higher molecular weight, particularly the secondary and tertiary alcohols. 5. It is suggested that release occurs in response to low alcohol concentrations altering the nature of the water-cell membrane interface, thus producing changes in membrane protein configuration and activation of phospholipase A. Inhibition of release is probably a consequence of non-specific depression of cell function.