Studies on pyrazinoylguanidine. 4. Upregulation of phosphodiesterase activity in rat adipose tissue and downregulation of gluconeogenesis and adenosine 3',5'-monophosphate concentrations in perfused rat liver.
In isolated rat adipocytes stimulated with theophylline (1 mmol/l), pyrazinoylguanidine (PZG) downregulated both lipolysis and cyclic AMP concentrations, raising the possibility that PZG stimulates adipose insulin-sensitive phosphodiesterase. To investigate this directly, we measured PZG's effects on phosphodiesterase activity in rat adipocytes. PZG (10 mumol/l) as well as insulin (0.1-1 mU) increased adipose phosphodiesterase activity, whereas theophylline reduced it. Also investigated were PZG's effects on gluconeogenesis and cyclic AMP in perfused rat liver where PZG decreased gluconeogenesis and cyclic AMP concentrations.
A-Rahim
Y I
YI
Department of Pharmacology, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Rannels
S L
SL
Kimball
S R
SR
Beyer
K H
KH
Vesell
E S
ES
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D000242:Cyclic AMP / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D006146:Guanidines; D007004:Hypoglycemic Agents; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; C056104:2-pyrazinoylguanidine; D013806:Theophylline; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases