Abstract

The enzyme, 2′-3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) has been known for over fifty years. Nevertheless, the roles this membrane-bound enzyme play have yet to be described completely. Recently, there has been renewed interest in the study of this enzyme due to studies that suggest that CNPase plays a role in the mediation of cellular inflammatory responses in renal and nervous system tissues. Also, this enzyme, found in oligodendrocytes of the nervous system, has been reported to participate in significant regulatory changes associated with age which may be involved in age-related CNS degeneration. Consequently, development of CNPase inhibitors is of interest and should aid in the study of this, as yet, poorly understood enzyme. In this work we utilized a spectrophotometric enzyme assay to determine the effect a panel of organo-vanadium complexes had on isolated hamster myelin CNPase activity. Our group has now identified several potent in vitro CNPase inhibitors that could prove useful in clarifying the important roles of this enzyme.

Highlights

  • Since its discovery in rabbit central nervous system tissue in the 1960s, the physiological role of 2,3 -cyclic nucleotide phosphohydrolase (EC # 3.1.4.37; cyclic nucleotide -phosphodiesterase (CNPase); phosphodiesterase) has been uncertain [1]

  • Reports of CNPase involvement with the pathological demyelination of axon terminals seen in multiple sclerosis (MS) patients suggest this enzyme plays a role in the progression of this and other neurological disorders exhibiting demyelination [8]

  • Baburina et al [4] reported that this enzyme, found in oligodendrocytes of the nervous system, participates in significant regulatory changes associated with age which may be partially involved in age-related CNS degeneration

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Summary

Introduction

Since its discovery in rabbit central nervous system tissue in the 1960s, the physiological role of 2 ,3 -cyclic nucleotide phosphohydrolase (EC # 3.1.4.37; CNPase; phosphodiesterase) has been uncertain [1]. Reports of CNPase involvement with the pathological demyelination of axon terminals seen in multiple sclerosis (MS) patients suggest this enzyme plays a role in the progression of this and other neurological disorders exhibiting demyelination [8]. These results suggest an anti-inflammatory role of CNPase in injured central nervous system cells [10].

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