Collecting tubule cells

Grenier, F.C. (1986). Characteristics of renal collecting tubule cells in primary culture. Mineral Electrolyte Metab. 12 58-63. 

Aldosterone acts on the late distal tubules and collecting tubule cells by combining with an intracellular receptor which induces the formation of aldosterone induced protein, which promotes Na+ reabsorption and K+ secretion. 

ADH antagonists inhibit the effects of ADH in the collecting tubule. Both lithium and demeclocycline appear to reduce the formation of cyclic adenosine monophospate (cAMP) in response to ADH and also to interfere with the actions of cAMP in the collecting tubule cells. 

The effects of aluminofluoride complexes on the kidney were studied using glomerular mesangial cells, proximal tubular cells, and inner medullar collecting tubule cells of rat kidney. 

Spielman WS, Sonnenburg WK, Allen ML, Arend U, Gerozissis K, Smith WL. Immunodissection and culture of rabbit cortical collecting tubule cells. Am J Physiol 1986 251 F348-F357. 

Vasopressin activates adenylate cyclase, which results in an increase in the production of cyclic adenosine monophosphate (cAMP). This results in enzymatic phosphorylation of channels in the membrane of the collecting tubule cells, allowing water to be reabsorbed from the urine. 

Figure 15-6. Mechanisms of sodium, potassium, and hydrogen ion movement and water reabsorption in the collecting tubule cells. Synthesis of Na+/K+ ATPase and sodium and potassium channels is under the control of aldosterone, which combines with an intracellular receptor, R, before entering the nucleus. ADH acts on its receptor, V, to facilitate the insertion of water channels from storage vesicles into the luminal membrane. (Reproduced, with permission, from Katzung BG [editor] Basic Clinical Pharmacology, 8th ed. McGraw-Hill, 2001.)...

The most predominant primary effects of mineralocorticoids are adequately observed upon the cortical collecting tubule cells strategically positioned in the kidneys to enhance substantially sodium reabsorption vis-a-vis potassium secretion. This eventually leads to an elevated aldosterone titer values that actually governs, controls, and monitors effectively sodium retention and potassium depletion thereby giving rise to volume expansion and weight gain, metabolic alkalosis, and hypertension. 

Garcia-Perez, A. and Smith, W.L. (1983). Use of monoclonal antibodies to isolate cortical collecting tubule cells AVP induces PC E release. Am. ]. Physiol, 244, C211-C220... 

Grenier, F.C., Rollins, T.E. and Smith W.L. (1981). Kinin-induced prostaglandin synthesis by renal papillary collecting tubule cells in culture. Am. ]. Physiol, 241, F94-F104... 

Pugliese, F., Sato, M., Williams, S., Aikawa, M., Hassid, A. and Dunn, M. (1983). Rabbit and rat renal papillary collecting tubule cells in culture The interactions of arginine vasopressin, prostaglandins and cyclic AMP. In Samuelsson, B., Ramwell, P.W. and Paoletti, R. (eds.) Advances in Prostaglandin, Thromboxane and Leukotriene Research, pp.517-23. (New York Raven Press)... 

Except for its lower protein concentration, glomerular filtrate at the top of the nephron is chemically identical to the plasma. The chemical composition of the urine is however quantitatively very different to that of plasma, the difference is due to the actions of the tubules. Cells of the proximal convoluted tubule (PCT) are responsible for bulk transfer and reclamation of most of the filtered water, sodium, amino acids and glucose (for example) whereas the distal convoluted tubule (DCT) and the collecting duct are concerned more with fine tuning the composition to suit the needs of the body. 

Sodium reabsorption Much less than 10% of the filtered load of NaCl reaches the distal nephron. Regulation of Na uptake, occurring mainly in the principal cells of the cortical collecting tubule, is controlled by the steroid hormone aldosterone (see Section 4.4). The net effect of aldosterone is the reclamation of NaCl and potassium excretion in to the luminal fluid. 

Water. Water resorption in the proximal tubule is a passive process in which water follows the osmotically active particles, particularly the Na" ions. Fine regulation of water excretion (diuresis) takes place in the collecting ducts, where the peptide hormone vasopressin (antidiuretic hormone, ADH) operates. This promotes recovery of water by stimulating the transfer of aquaporins (see p. 220) into the plasma membrane of the tubule cells via V2 receptors. A lack of ADH leads to the disease picture of diabetes insipidus, in which up to 30 L of final urine is produced per day. 

The mechanism by which Na" is reabsorbed in coupled exchange with and K+ in the collecting duct has been discussed previously that is, Na+-driven K+ secretion is partially under mineralocorticoid control. Aldosterone and other compounds with mineralocorticoid activity bind to a specific mineralocorticoid receptor in the cytoplasm of late distal tubule cells and of principal cells of the collecting ducts. This hormone-receptor complex is transported to the cell nucleus, where it induces synthesis of multiple proteins that are collectively called aldosterone-induced proteins. The precise mechanisms by which these proteins enhance Na+ transport are incompletely understood. However, the net effect is to increase Na" entry across apical cell membranes and to increase basolateral membrane Na+-K+-ATPase activity and synthesis. 

Figure 12.6 Mechanism of action of mineralocortjcoid receptor antagonists in the collecting tubule. Aldosterone enters the tubular cell by the basolateral surface and binds to a specific mineralocorticoid receptor (MNR) in the cytoplasm. The hormone receptor complex triggers the production of an aldosterone-induced protein (AlP) by the cell nucleus (NUC). The AIP acts on the sodium ion channel (ic) to augment the transport of Na+across the basolateral membrane and in to the cell. An increase in AIP activity leads to the recruitment of dormant sodium ion channels and Na pumps (P) in the cell membrane. AIP also leads to the synthesis of new channels and pumps within the cell. The increase in Na+conductance causes electrical changes in the luminal membrane that favour the excretion of intracellular cations, such as K+and H-h. Spironolactone competes with aldosterone for the binding site on the MNR and forms a complex which does not excite the production of AIP by the nucleus.

Acidosis and alkalosis are infrequent. Metabolic acidosis is a side effect of acetazolamide therapy and is due to bicarbonate loss in the PCT. All the K+-sparing diuretics can cause metabolic acidosis by H+ retention in the cells of the collecting duct. Metabolic alkalosis is associated with the loop and thiazide drugs. Reflex responses to volume depletion cause reabsorption of HCO-3 in the PCT and H+ secretion in the collecting tubule. 

Ion transport pathways across the luminal and basolateral membranes of collecting tubule and collecting duct cells. Inward diffusion of Na+ via the epithelial sodium channel (ENaC) leaves a lumen-negative potential, which drives reabsorption of and efflux of K+. (R, aldosterone receptor.)... 

Vasopressin activates two subtypes of G protein-coupled receptors (see Chapter 17). Vi receptors are found on vascular smooth muscle cells and mediate vasoconstriction. V2 receptors are found on renal tubule cells and reduce diuresis through increased water permeability and water resorption in the collecting tubules. Extrarenal V2-like receptors regulate the release of coagulation factor VIII and von Willebrand factor. 

A key determinant of the final urine concentration is antidiuretic hormone (ADH also called vasopressin). In the absence of ADH, the collecting tubule (and duct) is impermeable to water, and dilute urine is produced. However, membrane water permeability of principal cells can be increased by ADH-induced fusion of vesicles containing preformed water channels with the apical membranes (Figure 15-6). ADH secretion is regulated by serum osmolality and by volume status. 

Mineralocorticoids act by binding to the mineralocorticoid receptor in the cytoplasm of target cells, especially principal cells of the distal convoluted and collecting tubules of the kidney. The drug-receptor complex activates a series of events similar to those described above for the glucocorticoids and illustrated in Figure 39-3. It is of interest that this receptor has the same affinity for cortisol, which is present in much higher concentrations in the extracellular fluid. The specificity for mineralocorticoids at this site appears to be conferred, at least in part, by the presence of the... 

Figure 12.1 Schematic of a single nephron, the functional unit of the kidney. Microsolutes are filtered from blood cells in Bowman s capsules. As the filtrate passes towards the collection tubule most of the microsolutes and water are reabsorbed by a type of facilitated transport process. The fluid finally entering the collecting tubule contains the nitrogenous wastes from the body and is excreted as urine. There are about 1 million nephrons in the normal kidney [1]...

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