STUDIES ON PYRAZINOYLGUANIDINE .3. DOWN-REGULATION OF LIPOLYSIS IN ISOLATED ADIPOCYTES

The effects of pyrazinoylguanidine (PZG) on lipolysis and intracellula r cyclic AMP concentrations were investigated in isolated rat adipocyt es, PZG reduced basal cyclic AMP concentrations and blocked in a conce ntration-dependent manner forskolin (1 mu mol/l) and isoproterenol (1 mu mol/l) stimulatory effects on intracellular cyclic AMP production a nd lipolysis. PZG's effects on hormone-sensitive lipase were investiga ted in the presence and absence of glucagon (1 mu mol/l) or isoprotere nol (1 mu mol/l). PZG inhibited uncompetitively the induction of hormo ne-sensitive lipase by either glucagon or isoproterenol. PZG's antilip olytic effects appeared to result from downregulation of intracellular cyclic AMP concentrations, In adipose tissue, cyclic AMP controls lip olysis through hormone-sensitive lipase. PZG's downregulation of lipol ysis and cyclic AMP concentrations was unaffected by adenosine deamina se or pertussis toxin, suggesting that PZG did not activate G(i), the inhibitory guanyl nucleotide regulatory protein.