Tissue distribution and selective inhibition of subtypes of high affinity cAMP phosphodiesterase

High affinity cAMP phosphodiesterase (PDE), also referred to as PDE III, or low Km PDE occurs as two subtypes. One subtype is sensitive to inhibition by cGMP while the other is relatively insensitive. To be consistent with previously recommended nomenclature, these subtypes were designated Types IV...

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Bibliographic Details
Published inBiochemical pharmacology Vol. 37; no. 17; p. 3267
Main Authors Kariya, T, Dage, R C
Format Journal Article
LanguageEnglish
Published England 01.09.1988
Subjects
3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors
3',5'-Cyclic-AMP Phosphodiesterases - classification
3',5'-Cyclic-AMP Phosphodiesterases - metabolism
Animals
Brain - enzymology
Dogs
Female
Kidney - enzymology
Male
Myocardium - enzymology
Rats
Tissue Distribution
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Summary:High affinity cAMP phosphodiesterase (PDE), also referred to as PDE III, or low Km PDE occurs as two subtypes. One subtype is sensitive to inhibition by cGMP while the other is relatively insensitive. To be consistent with previously recommended nomenclature, these subtypes were designated Types IV and V PDEs respectively. Tissue distribution of these subtypes of high affinity cAMP PDE was investigated using comparative potencies of specific inhibitors. Of the tissues examined, dog heart contained the highest proportion of the cGMP inhibitable form (Type IV PDE), whereas dog kidney cortex and brain were composed almost entirely of the cGMP non-inhibitable form (Type V PDE). Enoximone and other new cardiotonic drugs that inhibit high affinity cAMP PDE were shown to be specific for the cGMP inhibitable form, whereas rolipram was specific for the cGMP non-inhibitable form. The apparently partially competitive kinetics shown by one of these drugs, enoximone, was due to the presence of both subtypes of the enzyme. When the activity of the cGMP non-inhibitable form was suppressed by rolipram, competitive inhibition of the cGMP inhibitable subtype by enoximone was observed. Rat heart high affinity cAMP PDE activity contained a higher proportion of the cGMP non-inhibitable subtype than did the enzyme from dog heart. It is suggested that this may account for the relative insensitivity of rats to the cardiotonic PDE inhibitors.
ISSN:0006-2952
DOI:10.1016/0006-2952(88)90637-5