INVOLVEMENT OF THE RAPID INCREASE IN CAMP CONTENT IN THE VANADATE-STIMULATED RELEASE OF LIPOPROTEIN-LIPASE ACTIVITY FROM RAT FAT PADS

Mechanisms of the stimulatory release of lipoprotein lipase (LPL) acti vity from isolated rat fat pads by sodium orthovanadate (vanadate) wer e studied through a cAMP-dependent process. A potent inhibitor of insu lin receptor tyrosine kinase, quercetin, inhibited the vanadate-increa sing effect on the LPL activity in fat pads, but did not inhibit the v anadate-stimulated release of LPL activity from the fat pads. Proprano lol and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8) decre ased the vanadate-stimulated release in a dose-dependent manner. Isopr oterenol and dibutyryl cAMP (Bt(2)cAMP) stimulated the release of LPL activity from fat pads. Vanadate, as well as isoproterenol, rapidly in creased the cAMP content in fat pads, and this increase was almost com pletely inhibited by propranolol. Vanadate increased the cAMP-dependen t protein kinase (PKA) activity ratios calculated from the measurement in the presence or absence of cAMP or PKA inhibitor. These results su ggest that the vanadate-stimulated release of LPL activity is associat ed with a process involving a rapid increase in the cAMP content accom panied by the activation of PKA.