-transparent.png){kind=logo}
Several previous studies have demonstrated that the phosphodiesterase 4 selective inhibitor rolipram affects cellular function at a much lower concentration than the reported Ki 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 microM of rolipram, indicating the presence of phosphodiesterase 4 in these fractions. The IC50 of rolipram (racemate) of these two fractions was 492 and 79 nM, respectively. The R-(-)-enantiomer of rolipram inhibited the cAMP-phosphodiesterase activity in the latter fraction 10 times more than did S-(+)-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 Ki 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.
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
January 2006,
Journal of bone and mineral metabolism,
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
July 1995,
European journal of pharmacology,
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
December 2012,
Urology,
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
July 2005,
NeuroImage,
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
July 2022,
Neurogastroenterology and motility,
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
November 2001,
Psychopharmacology,
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
July 2000,
European journal of pharmacology,
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
August 1993,
British journal of pharmacology,
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
December 1990,
Naunyn-Schmiedeberg's archives of pharmacology,
F Ohsawa, and
M Yamauchi, and
H Nagaso, and
S Murakami, and
J Baba, and
A Sawa
January 1997,
Journal of neural transmission (Vienna, Austria : 1996),
