Chlorpromazine and hormonal elevation of cyclic AMP contents in turkey erythrocytes and in perfused rat heart and liver

An investigation was carried out to determine whether chlorpromazine (CPZ) affected the elevation of cyclic AMP by isoprenaline in turkey erythrocytes and perfused rat hearts, and by glucagon in perfused rat liver. In the perfused heart, the incorporatiion of 14C-adenine (in the perfusate) into the cyclic AMP pool was also measured. In turkey erythrocytes exposed to isoprenaline, the cyclic AMP accumulation was markedly inhibited by CPZ at concentrations above 5 x 10-5 M, whereas lower concentrations caused slight reduction of cyclic AMP elevation. In the perfused rat heart and liver, CPZ at concentrations compatible with the integrity of the organ, did not reduce or change the cyclic AMP increase after isoprenaline and glucagon, respectively. The results indicate that inhibition of adenylate cyclase activation is not a general feature of the membrane stabilizing effects of CPZ. The loss of cyclic AMP response in turkey erythrocytes exposed to high concentrations of CPZ may be related to impairment of the cell membrane. CPZ could not be used as a tool in an attempt to discriminate between cyclic AMP-mediated and cyclic AMP-independent hormone effects. The present results compared to results obtained by other investigators indicate that caution is needed in extrapolating from experiments done on cell fractions to intact tissue. (author)