Inhibition of adipocyte lipolysis by papaverine: Papaverine can inhibit the redistribution of hormone-sensitive lipase

Papaverine, despite being a potent phosodiesterase inhibitor, actually bloc ks adipocyte lipolysis. The present study was designed to clarify the mecha nism of the inhibitory effect of papaverine on lipolysis. Lipolysis, stimul ated by either 10 mu M isoproterenol or 5 mM dibutyryl cAMP was significant ly inhibited by papaverine (100 mu M and above). Papaverine, however, did n ot affect the isoproterenol-induced increase in the protein kinase A (A-kin ase) activity ratio. In cell-free extract from non-stimulated adipocytes, c AMP-stimulated A-kinase activities were almost completely blocked by H-89, a potent inhibitor of A-kinase, but not by papaverine. Thus, the inhibitory effect of papaverine on lipolysis could be responsible for a deficit in st ep(s) distal to A-kinase activity. Hormone-sensitive lipase activities in t he infranatant fraction of centrifuged homogenates of cells, which were max imally stimulated with isoproterenol were significantly reduced. This resul t indicates that hormone-sensitive lipase redistributes from cytosol to its substrate in lipolytically stimulated cells. Papaverine completely blocked the isoproterenol-induced decrease in lipase activity in the infranatant f raction. These results suggest that papaverine blocks lipolysis through its inhibitory effect on the redistribution of hormone sensitive lipase. (C) 2 000 Elsevier Science Inc.