Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine whether the relatively selective inhibition of hepatic cholesterol synthesis by the hydrophilic 3-hydroxyl-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor pravastatin in vivo may be due to the existence of a specific uptake mechanism in the liver, the uptake by isolated rat hepatocytes was investigated. The uptake was composed of a saturable component [Michaelis constant (Km) 29 microM, maximal uptake rate 546 pmol.min-1.mg-1] and nonspecific diffusion (nonspecific uptake clearance 1.6 microliters.min-1.mg-1), inhibited by hypothermia, metabolic inhibitors, sulfhydryl-modifying reagents, and inhibitor of anion exchanger, whereas replacement of Na+ by choline+ or Cl- by gluconate- did not alter the uptake. Competitive inhibition was observed by a more highly lipophilic HMG-CoA reductase inhibitor simvastatin (open acid form), dibromosulfophthalein, cholate, and taurocholate. Pravastatin inhibited Na(+)-independent taurocholate uptake with an inhibition constant comparable with the Km value of pravastatin itself. Furthermore, the hepatic permeability clearance in vivo obtained with intact rats was comparable with that in vitro, indicating that the carrier-mediated active transport system we demonstrated in vitro is responsible for the hepatic uptake in vivo. These findings demonstrated that the hepatic uptake of pravastatin occurs via a carrier-mediated active transport mechanism utilizing the so-called multispecific anion transporter, which is common with the Na(+)-independent bile acid uptake system, and that this is one of the mechanisms for its selective inhibition of hepatic cholesterol synthesis in vivo.
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PMID:Na(+)-independent multispecific anion transporter mediates active transport of pravastatin into rat liver. 843 Aug 3

Cold preservation of kidneys is commonly used in human transplantation and in vitro studies. However, although disruption of the cytoskeleton by cold has been demonstrated in cultured cells, the effect of cold treatment on intact kidney is poorly understood. In this study, specific antibodies were used to examine the effect of hypothermia on the cytoskeletal network and the trafficking of some membrane proteins in the urinary tubule. Rat kidneys were cut into thin slices (approximately 0.5 mm) that were divided into several groups: (1) some were immediately fixed in paraformaldehyde, sodium periodate, and lysine (PLP); (2) some were stored at 4 degrees C for 15 min or 4 h before being fixed in cold PLP; or (3) after 4 h cold treatment, some slices were rewarmed to 37 degrees C for 15, 30, and 60 min in a physiologic solution, pH 7.4, and were then fixed in warm PLP. Immunofluorescence staining revealed an almost complete disruption of the microtubule network in proximal tubules after 15 min cold treatment, whereas microtubules in other segments were affected after 4 h. A partial recovery of the microtubule network was observed after 60 min rewarming. In contrast, actin filaments seemed to be resistant to cold treatment. gp330, aquaporin-2, H+ ATPase, and the AE1 anion exchanger were all relocated into numerous vesicles that were distributed throughout the cytoplasm after hypothermia followed by rewarming, whereas Na-K-ATPase retained its basolateral localization. The vasopressin-stimulated insertion of aquaporin-2 water channels into the apical membrane was inhibited during the initial rewarming period after cold exposure. Thus, cold preservation of tissues might impair, at least transiently, the polarized membrane expression and function of some transport proteins in renal epithelial cells.
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PMID:Cold-induced microtubule disruption and relocalization of membrane proteins in kidney epithelial cells. 952 91