Paper Information

Title: 

PHYSIOLOGICAL ROLES OF PDE3 ISOENZYMES AND PHARMACOLOGICAL EFFECTS OF THEIR SELECTIVE INHIBITORS

Type: PAPER
Author(s): SHAFIEINIK R.*
 
 *PHARMACOLOGY DEPARTMENT, MASHHAD UNIVERSITY OF MEDICAL SCIENCES
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Cyclic nucleotide phosphodiesterase enzymes (PDEs) have important roles in regulation of cAMP- and cGMP-mediated signaling systems. So far, more than 50 PDE have been characterized and categorized into 11 families (PDE1- PDE11). They have different amino acid sequences, biochemical characteristics and pharmacological properties. PDE3 family binds cAMP and cGMP with high affinity, but in the presence of cGMP the hydrolysis of cAMP is inhibited. Two PDE3 genes have been discovered: PDE3A is expressed primarily in cardiovascular cells and platelets, whereas PDE3B is expressed primarily in adipocytes, hepatocytes and pancreatic islets. In cardiovascular system, selective inhibition of PDE3 increases cardiac contractility, decreases peripheral vascular resistance and reduces platelet aggregation. Therefore, numerous agents with selective PDE3 inhibitory effect have been synthesized and used in clinical trial. In addition, application of these dugs in asthma results in relaxation of bronchial muscles and reduction of inflammation. However, the evidences show that, long term application of these drugs increases mortality which may be the result of their effects on metabolism. PDE3 has a functional role in regulation of cAMP-dependent signaling system in hepatocytes, adipocytes and insulin secreting cells. Selective PDE3 inhibitors increase gluconeogenesis, glycogenolysis, lipolysis and glucose-induced insulin secretion. In fasted and diabetic animals, administration of these drugs increases blood sugar, while in normal animal with hyperglycemia these drugs reduce levels of glucose in plasma and change growth pattern. However, the effects of these drugs in cardio-vascular and metabolism systems are variable and it is possible that the effects of these drugs are tissue-and species-dependent.

 
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