ATP-dependent leukotriene export from mastocytoma cells

AbstractThe biosynthesis of leukotrienes (LT) C4 and B4 is followed by an export of these mediators into the extracellular space. This transport was characterized using plasma membrane vesicles prepared from mastocytoma cells and identified as an ATP-dependent primary active process. The apparent Km-values were 110 nM for LTC4 and 48 μM for ATP. The transport rate was highest for LTC4, whereas LTD4, LTE4, and N-acetyl-LTE4 were transported with relative rates of 31, 12 and 8%, respectively, at a concentation of 10nM. LTB4 transport was also dependent on ATP, LTC4 transport with inhibited by LTD4 receptor antagonists (IC10 = 1.0 μM for MK-571 and 1.3 μM for LY245769) and by the inhibitor of leukotriene biosynthesis MK-886 (IC10 = 1.8 μM). The ATP-dependent export carrier for leukotrienes in leukotriene-synthesizing cells represents a novel member of the family of ATP-dependent exit pumps

Cyclic AMP stimulates sorting of the canalicular organic anion transporter (Mrp2/cMoat) to the apical domain in hepatocyte couplets

The canalicular membrane of rat hepatocytes contains an ATP-dependent multispecific organic anion transporter, also named multidrug resistance protein 2, that is responsible for the biliary secretion of several amphiphilic organic anions. This transport function is markedly diminished in mutant rats that lack the transport protein. To assess the role of vesicle traffic in the regulation of canalicular organic anion transport, we have examined the redistribution of the transporter to the canalicular membrane and the effect of cAMP on this process in isolated hepatocyte couplets, which retain secretory polarity. The partial disruption of cell-cell contact, due to the isolation procedure, leaves the couplet with both remnant apical membranes, as a source of apical proteins, and an intact apical domain and lumen, to which these proteins are targeted. The changes in distribution of the transporter were correlated to the apical excretion of a fluorescent substrate, glutathione-methyfluorescein. The data obtained in this study show that the transport protein, endocytosed from apical membrane remnants, first is redistributed along the basolateral plasma membrane. Then it is transcytosed to the remaining apical pole in a microtubule-dependent fashion, followed by the fusion of transporter-containing vesicles with the apical membrane. The cAMP analog dibutyrylcAMP stimulates all three steps, resulting in increased apically located transport protein, glutathione-methylfluorescein transport activity and apical membrane circumference. These findings indicate that the organic anion transport capacity of the apical membrane in hepatocyte couplets is regulated by cAMP-stimulated sorting of the multidrug resistance protein 2 to the apical membrane. The relevance of this phenomenon for the intact liver is discussed

Joint-Level Control of the DLR Lightweight Robot SARA

Lightweight robots are known to be intrinsically elastic in their joints. The established classical approaches to control such systems are mostly based on motor-side coordinates since the joints are comparatively stiff. However, that inevitably introduces errors in the coordinates that actually matter: the ones on the link side. Here we present a new joint-torque controller that uses feedback of the link-side positions. Passivity during interaction with the environment is formally shown as well as asymptotic stability of the desired equilibrium in the regulation case. The performance of the control approach is experimentally validated on DLR’s new generation of lightweight robots, namely the SARA robot, which enables this step from motor-side-based to link-sided-based control due to sensors with higher resolution and improved sampling rate

Simultaneous Motion Tracking and Joint Stiffness Control of Bidirectional Antagonistic Variable-Stiffness Actuators

Since safe human-robot interaction is naturally linked to compliance in these robots, this requirement presents a challenge for the positioning accuracy. The class of variable- stiffness robots features intrinsically soft contact behavior where the physical stiffness can even be altered during operation. Here we present a control scheme for bidirectional, antagonistic variable-stiffness actuators that achieve high-precision link-side trajectory tracking while simultaneously ensuring compliance during physical contact. Furthermore, the approach enables to regulate the pretension in the antagonism. The theoretical claims are confirmed by formal analyses of passivity during physical interaction and the proof of uniform asymptotic stability of the desired link-side trajectories. Experiments on the forearm joint of the DLR robot David verify the proposed approach