Methylxanthine and non-xanthine phosphodiesterase inhibitors. Their effects on adenosine uptake and the low Km cyclic AMP phosphodiesterase in intact rat adipocyte

• Published in: Biochemical pharmacology Vol. 34; no. 16; p. 2891
• Main Authors: Wong, E H, Ooi, S O
• Format: Journal Article
• Language: English
• Published: England 15.08.1985
• Subjects: 1-Methyl-3-isobutylxanthine - pharmacology; 3',5'-Cyclic-AMP Phosphodiesterases - antagonists & inhibitors; Adenosine - metabolism; Adenosine - pharmacology; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animals; Dipyridamole - pharmacology; Guanosine Triphosphate - pharmacology; In Vitro Techniques; Insulin - pharmacology; Kinetics; Lipolysis - drug effects; Male; Papaverine - pharmacology; Rats; Rats, Inbred Strains; Xanthines - pharmacology
• ISSN: 0006-2952
• DOI: 10.1016/0006-2952(85)90012-7

The effects of methylxanthines and non-xanthine phosphodiesterase-inhibitors on the low Km cyclic AMP phosphodiesterase of intact rat adipocytes were studied. Methylxanthines and papaverine stimulated rather than inhibited the enzyme when intact adipocytes were incubated in their presence. The effect of papaverine was not abolished by adenosine deaminase and was enhanced by adenosine. On the other hand, the effect of xanthine inhibitors and adenosine do not enhance each other. The difference in behaviour of these inhibitors could not be explained by their effects on adenosine uptake at the concentrations studied. Both agents inhibited adenosine uptake when measured after 15 sec and 10 min, with methylisobutylxanthine (MIX) having a greater inhibitory effect than papaverine only if uptake was measured after 15 sec. Effects similar to that of adenosine with the inhibitors on phosphodiesterase were obtained with insulin, which has been shown to act through a similar or related mechanism to that of adenosine. This was not the case with lipolytic agents whose effects were not potentiated by either MIX or papaverine. Under certain conditions the degree of stimulation of the enzyme was in fact decreased. Thus lipolytic and antilipolytic agents probably stimulated phosphodiesterase through distinct mechanisms.