Hormonal regulation of (Na+,K+)-ATPase biosynthesis in the toad bladder. Effect of aldosterone and 3,5,3'-triiodo-L-thyronine.

Body fat and body weight reduction following hypothalamic deep brain stimulation in monkeys: an intraventricular approach

Body fat and body weight reduction following hypothalamic deep brain stimulation in monkeys: an intraventricular approach.

Publisher Summary The sodium- and potassium-dependent adenosinetriphosphatase Na + , K + -ATPase (ATP phosphohydrolase) is a plasma membrane protein, which has been identified as the enzymatic expression of the sodium pump. Na + , K + -ATPase serves two functions—the extrusion of sodium out of the intracellular compartment and the accumulation of potassium into the same compartment. The cell devotes a large fraction (2–40%) of its ATP production for this single function. In the most extreme cases (epithelial cells), up to 70% of the oxydative metabolism can be coupled to obtain sensitive sodium and potassium transport. Therefore, this process plays a critical role in the homeostasis of sodium and potassium not only in the intracellular but also in the extracellular milieu. In all cells, Na + , K + -ATPase maintains a high intracellular K + concentration required for the macromolecule biosynthesis machinery. In epithelial cells, Na + , K + -ATPase is one of the major factors allowing transcellular salt transport, thereby controlling the osmolarity of the extracellular compartment. Epithelia are, therefore, able to create and maintain a large hydro osmotic gradient between the extracellular space and the external environment.

Chapter 7 Biosynthesis of Na+, K+-ATPase in Amphibian Epithelial Cells

Publisher Summary This chapter discusses the regulation of Na, K–ATPase by its biosynthesis and turnover. The regulation of alkali cation transport in a cell or tissue is in general brought about by the interaction of two processes: modulation of the number of copies of Na, K–ATPase and modulation of the activity of existing copies by appropriate ligands and substrates. Na, K–ATPase is a very dynamic protein. It is constantly being synthesized and turned over in many tissues and is susceptible to up and down regulation in number of copies in response to a variety of environmental stimuli. In the biosynthesis of this enzyme membrane and secretory proteins are generally believed to be synthesized in the rough endoplasmic reticulum (RER), being cotranslationally inserted partially (membrane proteins) or completely (secretory proteins) into the lumen of the RER. In the chapter, the small hydrophobic signal sequence is removed and common oligosaccharide precursors are transferred to the peptide backbone. RER-derived vesicles containing these proteins are then shuttled to the Golgi apparatus for further processing occurs. The proteins are then sorted via some unknown process and transferred to specific organelles, or in the case of secretory products, exported out of the cell by exocytosis. The translocation and covalent modification of the proteins accounts for a several-hour lag or “transit” time between translation and the arrival at their functional destination.

Regulation of Na,K-ATPase by Its Biosynthesis and Turnover

Aldosterone increases transepithelial Na+ transport in the urinary bladder ofBufo marinus. The response is characterized by 3 distinct phases: 1) a lag period of about 60 min, ii) an initial phase (early response) of about 2 hr during which Na+ transport increases rapidly and transepithelial electrical resistance falls, and iii) a late phase (late response) of about 4 to 6 hr during which Na+ transport still increases significantly but with very little change in resistance. Triiodothyronine (T3, 6nm) added either 2 or 18 hr before aldosterone selectively antagonizes the late response. T3per se (up to 6nm) has no effect on base-line Na+ transport. The antagonist activity of T3 is only apparent after a latent period of about 6 to 8 hr. It is not rapidly reversible after a 4-hr washout of the hormone. The effects appear to be selective for thyromimetic drugs since reverse T3 (rT3) is inactive and isopropyldiiodothyronine (isoT2) is more active than T3. The relative activity of these analogs corresponds to their relative affinity for T3 nuclear binding sites which we have previously described. Our data suggest that T3 might control the expression of aldosterone by regulating gene expression, e.g. by the induction of specific proteins, which in turn will inhibit the late mineralocorticoid response, without interaction with the early response.

Effects of thyromimetric drugs on aldosterone-dependent sodium transport in the toad bladder

The effects of thyroxine (T4) on Na+ transport, oxygen consumption (QO2), and Na+-K+-ATPase activity were studied in the urinary bladder and liver of the toad Bufo marinus. In the bladder, T4 in vitro (10(-8) to 10(-6) M) had no significant effect on these parameters during 15 h of incubation. When injected intraperitoneally (approximately 20 microgram/(kg body wt.day) for 6 days), T4 lowered base-line, short-circuit current by 62% (P less than 0.0025) and potential difference by 37% (P less than 0.001), increasing tissue resistance by 40% (P less than 0.02). T4 depressed QO2/DNA (-25%, P less than 0.05) with no significant effect on Na+-K+-ATPase activity. In liver, T4 increased the recovery per cell DNA of mitochondrial proteins by 32% (P less than 0.025), corresponding to an increased QO2 (stage IV) of isolated mitochondria per cell DNA (+54%, P less than 0.01). There was no significant effect on Na+-K+-ATPase activity. These results suggest that, unlike its function in the rat, T4 in the toad does not regulate cellular thermogenesis by inducing Na+-K+-ATPase. This major difference could account at least in part for the transition from poikilothermy to homeothermy. In addition, T4 has a distinct inhibitory effect on Na+ transport in the urinary bladder, which suggests an antagonism to the action of aldosterone.

C. S. Lo

Papers

Thyroxine and Na+ transport in toad: role in transition from poikilo- to homeothermy.