Inhibitory Effects of Rolipram on Partially Purified Phosphodiesterase 4 From Rat Brains

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Author(s)

Abstract

Several previous studies have demonstrated that the phosphodiesterase 4 selective inhibitor rolipram affects cellular function at a much lower concentration than the reported K<SUB>i</SUB> value for phosphodiesterase 4 inhibition. In this study, we examined the inhibitory effect of rolipram on rat brain phosphodiesterase 4 to determine the heterogeneity of the enzyme activity. Partial purification of various phosphodiesterases from the rat brain was performed by anion-exchange chromatography. The eluant was pooled into four fractions, two of which manifested cAMP-selective phosphodiesterase activity that was blocked by 10 μM of rolipram, indicating the presence of phosphodiesterase 4 in these fractions. The IC<SUB>50</SUB> of rolipram (racemate) of these two fractions was 492 and 79 nM, respectively. The <I>R</I>-(-)-enantiomer of rolipram inhibited the cAMP-phosphodiesterase activity in the latter fraction 10 times more than did <I>S</I>-(+)-rolipram, and the inhibition of the former fraction was less stereospecific. Dixon plot analysis revealed that the rolipram enantiomers inhibited the cAMP-phosphodiesterase in the latter fraction in a multiphasic manner, with two K<SUB>i</SUB> values, one at the micromolar level and the other at the sub-micromolar level, respectively, for both of the enantiomers. These results suggest that there is a heterogeneity for phosphodiesterase 4 in the rat brain, and some of the phosphodiesterase forms are sensitive to rolipram.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 77(2), 147-154, 1998-06-01

    The Japanese Pharmacological Society

References:  29

Codes

  • NII Article ID (NAID)
    10008192985
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4514090
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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