Cyclic nucleotide phosphodiesterase 3 expression in vivo: evidence for tissue-specific expression of phosphodiesterase 3A or 3B mRNA and activity in the aorta and adipose tissue of atherosclerosis-prone insulin-resistant rats

Diabetes
T NagaokaY Fujita-Yamaguchi

Abstract

With a view of understanding the potential roles of phosphodiesterase (PDE)3 in the acceleration of atherosclerosis in diabetes, we have analyzed the in vivo levels of low Km cAMP PDE3 and PDE4 activities as well as PDE3A and PDE3B mRNA in a relevant animal model. The JCR:LA-cp rat is a unique strain that develops obesity, insulin resistance, and vasculopathy when homozygous for the autosomal recessive cp gene (cp/cp). Lean rats, bred (designated +/?) as a 2:1 mixture of animals that are heterozygous (cp/+) or homozygous normal (+/+), are metabolically normal. We find that PDE3 activity is the major low Km cAMP activity in the aorta of cp/cp rats and is approximately twofold higher than that in lean +/? rats. PDE3A mRNA levels in middle-aged cp/cp rats are also elevated, approximately threefold, compared with those of +/? rats or young 12-week-old cp/cp rats. Thus, in the aorta of atherosclerosis-prone insulin-resistant cp/cp rats, PDE3A gene expression is upregulated, resulting in significantly higher PDE3 activity. This upregulation of PDE3A mRNA levels was a rather unique phenomenon to the aorta of JCR:LA-cp rats compared with that in the aorta of other rat strains. This result is consistent with our hypothesis that an incre...Continue Reading

Citations

Mar 14, 2002·Diabetes, Obesity & Metabolism·David N Brindley, James C Russell
Feb 16, 2008·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Takayuki MatsumotoKatsuo Kamata
Mar 20, 2009·Canadian Journal of Physiology and Pharmacology·Michael GreeneJean N Dasilva
Dec 25, 2003·Journal of Smooth Muscle Research = Nihon Heikatsukin Gakkai Kikanshi·Takayuki MatsumotoKatsuo Kamata
Jan 3, 2007·Biochemical and Biophysical Research Communications·Alina OknianskaEva Degerman
Nov 26, 2010·Biochemical and Biophysical Research Communications·Tamotsu TsukaharaKimiko Murakami-Murofushi
May 24, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoKatsuo Kamata
May 10, 2006·The Journal of Pharmacology and Experimental Therapeutics·Takao FujimuraSeitaro Mutoh
May 17, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoKatsuo Kamata
Jun 10, 2003·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoKatsuo Kamata
May 8, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Takayuki MatsumotoKatsuo Kamata
Apr 4, 2020·Current Pharmaceutical Design·Javier Blanco-Rivero, Fabiano E Xavier
Aug 3, 2021·Life Sciences·Rita HannaAniella Abi-Gerges

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