Phosphodiesterase function and endocrine cells: links to human disease and roles in tumor development and treatment

Curr Opin Pharmacol. 2011 Dec;11(6):689-97. doi: 10.1016/j.coph.2011.10.003. Epub 2011 Oct 31.

Abstract

Phosphodiesterases (PDEs) are enzymes that regulate the intracellular levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate, and, consequently, exhibit a central role in multiple cellular functions. The pharmacological exploitation of the ability of PDEs to regulate specific pathways has led to the discovery of drugs with selective action against specific PDE isoforms. Considerable attention has been given to the development of selective PDE inhibitors, especially after the therapeutic success of PDE5 inhibitors in the treatment of erectile dysfunction. Several associations between PDE genes and genetic diseases have been described, and more recently PDE11A and PDE8B have been implicated in predisposition to tumor formation. This review focuses on the possible function of PDEs in a variety of tumors, primarily in endocrine glands, both in tumor predisposition and as potential therapeutic targets.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism*
  • 3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors
  • 3',5'-Cyclic-GMP Phosphodiesterases / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / physiology
  • Cyclic GMP / antagonists & inhibitors
  • Cyclic GMP / physiology
  • Endocrine Cells / drug effects
  • Endocrine Cells / enzymology*
  • Endocrine Cells / metabolism
  • Endocrine Gland Neoplasms / drug therapy*
  • Endocrine Gland Neoplasms / enzymology
  • Endocrine Gland Neoplasms / metabolism
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Molecular Targeted Therapy
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / therapeutic use*

Substances

  • Antineoplastic Agents
  • Isoenzymes
  • Neoplasm Proteins
  • Phosphodiesterase Inhibitors
  • Cyclic AMP
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic GMP