Prolyl endopeptidase (PEP) is a proline-specific oligopepti-dase with a reported effect on learning and memory in dif-ferent rat model systems. Using the astroglioma cell line U343,PEP expression was reduced by an antisense technique. Measuring different second-messenger concen-trations revealed an inverse correlation between inositol 1,4,5-triphosphate [Ins(1,4,5)P3] concentration and PEP expression in the generated antisense cell lines. However,no effect on cAMP generation was observed.