J. Lipid Res.
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Journal of Lipid Research, Vol 34, 1737-1743, Copyright © 1993 by Lipid Research, Inc.

ARTICLES

Effect of phosphodiesterase inhibition with amrinone or theophylline on lipolysis and blood flow in human adipose tissue in vivo as measured with microdialysis

P Arner, J Hellmer, E Hagstrom-Toft and J Bolinder
Department of Medicine, Huddinge Hospital, Karolinska Institute, Sweden.

Phosphodiesterase III (cyclic GMP-inhibited, particulate, low Km) is believed to play a dominant role in the cyclic AMP breakdown and lipolysis regulation in fat cells. Its importance for lipolysis activity was investigated in situ in humans by comparing the effects of a selective (amrinone) and a nonselective (theophylline) inhibitor of the enzyme. Abdominal subcutaneous adipose tissue of healthy nonobese humans was microdialyzed with solvents containing one or both of these agents, and glycerol (lipolysis index) or the escape of ethanol from the dialysis solvent (blood flow index) was continuously monitored in the perfusate. Both agents caused a dose-dependent and sustained increase in the glycerol level in the perfusate for at least 2.5 h. Although amrinone was 5000 times more potent than theophylline on a molar basis, its maximum activity was only 35% as compared to the maximum activity of theophylline. Half-maximum lipolytic effect of the two drugs occurred at about 0.1 mumol/l and 1 mmol/l, respectively (P < 0.001). At maximum effective concentrations, amrinone stimulated lipolysis by about 63% and theophylline by about 200% (P < 0.01). At these concentrations amrinone increased the rate of disappearance of ethanol from the perfusate by about 20% and theophylline increased the rate by about 75%, the difference being statistically significant (P < 0.01). When the two drugs were added together, the level of lipolysis stimulation was not different from that with theophylline alone both at maximal and submaximal effective concentrations of drug combinations.(ABSTRACT TRUNCATED AT 250 WORDS)
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P. B. Snyder, J. M. Esselstyn, K. Loughney, S. L. Wolda, and V. A. Florio
The role of cyclic nucleotide phosphodiesterases in the regulation of adipocyte lipolysis
J. Lipid Res., March 1, 2005; 46(3): 494 - 503.
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