Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B

The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA levels and induces insulin resistance, for which the...

C1 compounds as auxiliary substrate for engineered Pseudomonas putida S12

The solvent-tolerant bacterium Pseudomonas putida S12 was engineered to efficiently utilize the C1 compounds methanol and formaldehyde as auxiliary substrate. The hps and phi genes of Bacillus brevis, encoding two key steps of the ribulose monophosphate (RuMP) pathway, were introduced to construct a pathway for the metabolism of the toxic...

Adenosine 3':5'-cyclic monophosphate induces regulated secretion of tissue-type plasminogen activator and von Willebrand factor from cultured human endothelial cells

The effect of compounds increasing intracellular adenosine 3':5'cyclic monophosphate [cAMP](i) levels (prostacyclin. isoproterenol, forskolin, cholera toxin), and of the cAMP analogs 8-bromo-cAMP and dibutyrpl-cAMP, on the regulated secretion (acute release) of tissue-type plasminogen activator (tPA) and von Willebrand factor (vWF) was studied...

Transport of the glutathione conjugate of ethacrynic acid by the human multidrug resistance protein MRP

The multidrug resistance protein MRP has been shown to mediate the transport of glutathione S-conjugates across membranes. In this study we demonstrate that the glutathione S-conjugate of the diuretic drug ethacrynic acid, which is an efficient inhibitor of glutathione S-transferases, is a high-affinity substrate and inhibitor of the glutathione...

The role of cyclic nucleotides in the release of tissue-type plasminogen activator and von Willebrand factor

The modulation of the induced acute release of tissue-type plasminogen activator (t-PA) and of von Willebrand factor (vWF) by compounds affecting cyclic nucleotide levels was studied, using an isolated rat hindleg perfusion system. Platelet-activating factor (PAF; 5 nM) or bradykinin (0.8 μM) were used to induce release of t-PA and vWF. The...

On the role of bradykinin in secretion from vascular endothelial cells

Bradykinin will induce, in perfused rat hindlegs, the acute release from endothelial cells of tissue-type plasminogen activator and of von Willebrand factor. This release is mediated by B2-receptors, requires the influx of extracellular calcium, and is modulated by cyclic nucleotides. A possible role of bradykinin in the physiological regulation...

Effect of the acquisition enhancing drug piracetam on rat cerebral energy metabolism. Comparison with naftidrofuryl and methamphetamine

The effects of Piracetam, Naftidrofuryl and methamphetamine on several parameters of cerebral energy metabolism have been studied. At variance with some reports in the literature neither Piracetam nor Naftidrofuryl affected the cerebral contents of adenine nucleotides and, accordingly, both substances were without effect on the adenylate energy...