THE EFFECT OF SEROTONIN ON THE PHOSPHOLIPID FORMATION AND ON THE INCORPORATION OF PHOSPHATE INTO PHOSPHOLIPIDS IN RAT LIVER MITOCHONDRIA.

Abstract

Paper chromatographic determinations of mitochondrial phospholipid fractions revealed that increment of phosphoinositide was mainly responsible for the increase of total phospholipid content during the experimental incubation period. Serotonin creatinine sulfate (5×10-4M) prevented the increase of this particular fraction, and showed little influence on the content of other fractions.Requirement of Mg+2 for the active incorporation of inorganic phosphate into mitochondria and the counteractive action of Ca+2 upon this process were confirmed. Serotonin exerted a stimulation of phosphate uptake at the lower concentrations, e. g., 10-6M. At the higher concentrations of serotonin, a transient stimulation succeeded by an inhibition was observed. The serotonin effects were still demonstrable in Ca+2-eliminated test systems, showing that the effects could not solely be accounted for by a shift of Ca+2 within mitochondria.Fractionation of 32P-labelled mitochondrial phospholipid showed that phosphoinositide was the most rapidly labelled fraction. Inhibition of 32P incorporation by serotonin was also most evident in this fraction. The inhibition was counteracted by an addition of ATP, and an induction of ATPase by serotonin was confirmed. The labelling of phospholipids by 32P lagged behind that of ATP, and the specific activity of ATP was far greater than that of phospholipids.It has been concluded that the inhibition of phosphate incorporation into ATP must be the primary cause of the observed inhibitory effects of serotonin upon mitochondrial phospholipids.