Studies on pyrazinoylguanidine. 3. Downregulation of lipolysis in isolated adipocytes.
The effects of pyrazinoylguanidine (PZG) on lipolysis and intracellular cyclic AMP concentrations were investigated in isolated rat adipocytes. PZG reduced basal cyclic AMP concentrations and blocked in a concentration-dependent manner forskolin (1 mumol/l) and isoproterenol (1 mumol/l) stimulatory effects on intracellular cyclic AMP production and lipolysis. PZG's effects on hormone-sensitive lipase were investigated in the presence and absence of glucagon (1 mumol/l) or isoproterenol (1 mumol/l). PZG inhibited uncompetitively the induction of hormone-sensitive lipase by either glucagon or isoproterenol. PZG's antilipolytic effects appeared to result from downregulation of intracellular cyclic AMP concentrations. In adipose tissue, cyclic AMP controls lipolysis through hormone-sensitive lipase. PZG's downregulation of lipolysis and cyclic AMP concentrations was unaffected by adenosine deaminase or pertussis toxin, suggesting that PZG did not activate Gi, the inhibitory guanyl nucleotide regulatory protein.
A-Rahim
Y I
YI
Department of Pharmacology, Pennsylvania State University, College of Medicine, Hershey 17033, USA.
Beyer
K H
KH
Vesell
E S
ES
D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005990:Glycerol / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008049:Lipase / Q000032:analysis; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D037342:Pertussis Toxin; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D006146:Guanidines; D007004:Hypoglycemic Agents; D011719:Pyrazines; D010566:Virulence Factors, Bordetella; D005576:Colforsin; C056104:2-pyrazinoylguanidine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D008049:Lipase; D007545:Isoproterenol; D005990:Glycerol