Effects of Ethanol on Human Lymphocyte Levels of Cyclic AMP In Vitro: Potentiation of the Response to Isoproterenol, Prostaglandin E2 or Adenosine Stimulation

The effects of ethanol, acetone and dimethylsulfoxide (DMSO) were tested on the accumulation of cyclic AMP in human peripheral blood lymphocytes in vitro. Isoproterenol (1.0X10(-8) - 1.0X10(-4)M), PGE2 (3X10(-8)-3X10(-6)M), adenosine (10(-7) - 10(-4)M) and phenylisopropyladenosine (10(-8) - 10(-4)M) caused a dose dependent increase in cyclic AMP accumulation. Over the entire range of concentration of stimulating drugs, ethanol caused an enhanced accumulation of cyclic AMP. At temperatures between 15 degrees and 30 degrees the effect of ethanol rose with increasing concentration from 0.2-6%. At 37 degrees and 40 degrees, 6% ethanol had less stimulatory effect than 2% ethanol. The effect of ethanol was shared by acetone and to a minor extent by DMSO, and was present also when phosphodiesterase was inhibited by isobutylmethylxanthine. It is suggested that ethanol enhances adenylate cyclase activity as a consequence of altered cell membrane fluidity. Since the effects on cyclic AMP accumulation can be observed already at rather low concentration of the solvents they may be of toxicological significance.