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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epithelial cells from a variety of species and organs form polarized epithelia in culture. When epithelia are grown on a porous surface, such as a millipore filter, transport can be studied using adaptations of standard techniques. In the few years in which cultured epithelia have been studied by transport physiologists, most work has been focused on identification and description of the differentiated transport exhibited by cultured epithelia. Epithelia formed by a continuous line of cells derived from pig kidney (LLC-PK1) exhibit sodium-coupled glucose transport similar to that of the proximal tubule and have vasopressin-sensitive adenylate cyclase that has been studied in great detail. Also of interest are epithelia formed by continuous lines of cells derived from amphibian kidney (A6) and from amphibian urinary bladder (TBM). Each line forms epithelia that have high electrical resistance and amiloride-sensitive sodium transport. Transport is stimulated by aldosterone and by cAMP or hormones that raise cell cAMP levels. In LLC-PK1 and in A6 epithelia, transport and the response to hormones can be manipulated by manipulating the culture conditions. Cultured epithelia have also been used to explore the cell biology of epithelia. Most interesting in this regard are studies of the development and maintenance of epithelial cell polarity. This approach should be especially valuable.
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PMID:Use of cultured epithelia to study transport and its regulation. 631 89

The avian kidney contains reptilian-type (RT) nephrons that do not function in concert and mammalian-type (MT) nephrons that do function in concert to permit production of concentrated urine. Significant data on endocrine regulation of renal function are available only for antidiuretic hormone (arginine vasotocin, AVT) and parathyroid hormone (PTH). Plasma AVT increases and number of filtering RT nephrons decrease when plasma osmolality increases. Small doses of AVT reduce the number of filtering RT nephrons, and all RT nephrons filter following acute neurohypophysectomy. In addition to changing tubule permeability to water, AVT affects the concentrating mechanism by reducing the number of filtering RT nephrons and flow through collecting ducts. Both net tubular reabsorption and net tubular secretion of PO4 occur. Parathyroidectomy (PTX) stimulates PO4 reabsorption, and PTH replacement decreases reabsorption and stimulates secretion, apparently in proximal tubules of RT nephrons. PTX stimulates and PTH replacement inhibits Na-dependent PO4 transport by renal brush border membrane vesicles. PTH also stimulates Ca2+ reabsorption but apparently not long the proximal tubule of RT nephrons.
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PMID:Endocrine regulation of avian renal function. 639 8

Diuretics have a central role in the treatment of edema and hypertension. This function is primarily an induction of a net negative balance of solute and water. Reviewed herein are the transport properties of each nephron segment that governs salt and water reabsorption with specific reference to the mechanisms by which the various diuretic agents affect those transport processes. Under normal circumstances, the proximal tubule reabsorbs about 50 to 66 percent of the filtered fluid by both active and passive mechanisms. However, diuretics that inhibit proximal reabsorption are "weak" diuretics since distal compensatory mechanisms can overcome their effect. The thin descending limb of Henle is highly permeable to water and relatively impermeable to solutes. Thus, its main physiologic function is to allow osmotic water abstraction. Although diuretics have no direct epithelial effect on this segment, many of the diuretics decrease fluid reabsorption from it by abolishing the papillary osmotic gradient. The decreased water absorption from the descending limb of Henle has a major role in over-all increased diuresis since nephron segments distal to the descending limb are impermeable to water in the absence of vasopressin. The thin ascending limb of Henle is impermeable to water while being highly permeable to sodium and chloride. Diuretics have no direct effect on the thin ascending limb of Henle. The medullary and cortical segments of the thick ascending limb of Henle absorb sodium chloride by active mechanisms as a result of a secondary active chloride transport mechanism that depends on the presence of sodium (co-transport mechanism). This transport mechanism is located on the luminal membrane. Most of the "loop" diuretics effect this process from the luminal side by having a direct inhibitory effect on this co-transport process. The diuretics that have a primary effect on the medullary segment (furosemide, bumetanide, ethacrynic acid) inhibit the concentrating mechanisms, whereas the diuretics that are effective primarily in the cortical segment (thiazides plus the diuretics affecting the medullary segment) inhibit the urinary diluting mechanism. The loop diuretics are physiologically the most potent family of diuretics. The cortical collecting duct segment reabsorbs sodium by active mechanisms. These processes are stimulated by aldosterone. The diuretics that affect these processes are considered weak diuretics, but they do have the metabolic effect of potassium sparing.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Site and mechanism of action of diuretics. 649 55

Thromboxane B2 (TxB) is excreted in human urine, but the mechanism of renal excretion and the quantitative relationship of urinary TxB to the active parent compound, thromboxane A2, of renal or extrarenal origin is not established. To determine the effects of vasoactive hormones, uricosuric agents and urinary flow rate on TxB excretion, urinary TxB was measured by radioimmunoassay and mass spectrometry, and renal metabolism of blood TxB was determined by radiochromatography of urine after i.v. [3H]-TxB infusions. Basal TxB was 6.7 +/- 1.1 ng/h during an oral water load, and TxB fell with s.g. antidiuretic hormone (to 3.4 +/- 0.4 ng/h, P less than 0.01) and with fluid restriction (to 2.6 +/- 0.5 ng/hr, P = 0.001) in parallel with urinary volume. Urinary excretion of unmetabolized [3H]-TxB also fell (by 56%) with fluid restriction, implicating altered metabolism rather than synthesis as the mechanism of the urinary flow effect. Angiotensin II infusions slightly reduced both TxB and urine volume, consistent with a flow effect. In contrast, probenecid did not alter urine volume, but increased urinary uric acid (by 244%), TxB (from 5.6 +/- 0.9 to 11.1 +/- 2.9 ng/h) and urinary excretion of blood [3H]-TxB (by 243%) by similar amounts (all P less than 0.05), suggesting that TxB is actively reabsorbed in the proximal tubule, similarly to uric acid. Thus, urinary excretion of TxB of renal and extrarenal origin is regulated by proximal and distal tubule factors.
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PMID:Regulation of urinary thromboxane B2 in man: influence of urinary flow rate and tubular transport. 671 53

Filtered proteins including insulin are absorbed in the proximal tubule by means of pinocytosis. The first step in this process is binding of the protein to brush border membrane. As it is not known whether absorption exhibits specificity, we set out to determine whether specific binding sites for insulin are present in brush border membranes. Rabbit-isolated brush border membranes were incubated with 125I-insulin and varying concentrations of cold insulin or other peptide hormones. Binding and degradation of 125I-insulin occurred in a time- and temperature-dependent manner. Native insulin competitively inhibited 125I-insulin binding, but calcitonin, arginine vasopressin, glucagon, and growth hormone (10(-6) M) were relatively ineffective. Nonspecific binding averaged one-third of the total radioactivity bound. Scatchard analysis of binding data revealed two classes of insulin receptors: high affinity, low capacity receptors and low affinity, high capacity receptors. Gel filtration analysis of 125I-insulin exposed to brush border membrane revealed the formation of low-molecular-weight products similar to that produced by intact kidneys. The degrading process exhibited some specificity, for cold insulin (10(-6) M) was more effective than calcitonin, vasopressin, glucagon, or growth hormone in inhibiting degradation (32% versus less than 13% inhibition; P less than 0.01). Whether this reflects inhibition of insulin specific binding before exposure to degradation or inhibition of specific enzymes is unclear. In summary, it appears that renal brush border membranes have a major insulin-specific receptor component that could potentially mediate tubular insulin absorption. In addition, there is a smaller nonspecific component that may also have the potential to mediate insulin absorption. Finally, it appears that brush border membranes have the ability to degrade insulin to low-molecular-weight products by a process that exhibits some specificity for insulin.
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PMID:Binding and degradation of insulin by isolated renal brush border membranes. 676 Dec

Reabsorption and/or degradation of proteins or peptides are functions of the proximal tubule. Large polypeptides or proteins are reabsorbed by luminal endocytosis and hydrolyzed by lysosomal enzymes. Our recent studies indicate that small linear peptides are hydrolyzed at the luminal membrane, with reabsorption of metabolites. The renal transport and hydrolysis of radiolabeled Al, All, BKN, oxytocin, glucagon, insulin, and LHRH were studied. Techniques for in vivo microinfusion of surface tubules in rats, arterial infusion in filtering and nonfiltering rat kidneys in vivo, and in vitro microperfusion of isolated rabbit nephron segments were used. Reabsorption of radiolabeled material was measured and the intact peptide or its metabolites were identified and quantified in urine, renal venous blood, bathing medium, and/or collection fluid. In addition, peptides were incubated in the presence of isolated renal membrane preparations to identify a probably cellular site of hydrolysis. The findings indicate that in proximal, but not distal tubules, radiolabeled Al, All, BKN, glucagon, and LHRH are hydrolyzed by brush border enzymes at the luminal membrane, followed by reabsorption of metabolites. In addition, it was found that, similar to the small intestine, the proximal tubule reabsorbed small peptide fragments, which were further degraded intracellurarly, In vivo inhibition studies with excess peptides revealed that hydrolysis is a more specific process than studies with excess peptides revealed that hydrolysis is a more specific process than reabsorption of metabolites. Large or small, complex peptides like insulin, oxytocin, or vasopressin that contain disulfide bridges are not hydrolyzed at the luminal brush border of the proximal tubule. In vivo sequestration and slow degradation of insulin by rat tubules suggest that this peptide is reabsorbed by endocytosis and degraded in lysosomes. Thus, as the molecular complexity or weight of a peptide increases, the mechanism for renal tubular degradation, instead of depending on luminal membrane hydrolysis, may primarily involve endocytosis and lysosomal digestion. This recently described mechanism for hydrolysis and transport of small linear peptides in the proximal nephron is characterized by having a high capacity and is analogous to membrane hydrolysis described for intestinal microvilli. The process may be biologically important to (1) conserve amino acids, (2) inactivate toxic peptides, and (3) help regulate circulating levels of peptide hormones.
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PMID:Renal tubular processing of small peptide hormones. 704 58

1. The diffusional permeability of collecting ducts to 22Na+ and 36Cl- was measured in rat papillae in vitro. 2. The permeability of the collecting duct to 36Cl- was 0.72 (s.e.m. = 0.01; n = 356) microns/sec which was significantly higher than the value of 0.51 (s.e.m. = 0.01; n = 356) microns/sec measured for 22Na+. 3. Collecting ducts in papillae taken from rats on a high sodium intake had a 22Na+ permeability of 0.63 (s.e.m. = 0.04; n = 53) microns/sec which was significantly higher than the value on a normal salt intake (0.50, s.e.m. = 0.04; n = 46 microns/sec). 4. When papillae from normal rats were studied in plasma taken from salt loaded rats, the 22Na+ permeability of 0.59 (s.e.m. = 0.04; n = 18) microns/sec was significantly higher than when incubated in plasma from normal rats (0.44, s.e.m. = 0.05; n = 12) microns/sec. 5. An extract of urine with natriuretic activity had no effect on 22Na+ permeability when tested in this system. 6. Adrenalectomy, PGE2, indomethacin and antidiuretic hormone had no significant effect on 22Na+ and 36Cl- permeability. 7. A substance exists in plasma from salt loaded animals that increases the permeability of collecting ducts to sodium. This effect could explain the component of the natriuresis that follows saline infusion which is independent of changes in glomerular filtration rate, aldosterone, or proximal tubule reabsorption.
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PMID:The permeability of collecting ducts to 22Na+ and 36Cl- in rat isolated papillae. 716 10

Osmotic control for vasopressin release has been recognized for several years. Further understanding of factors affecting the sensitivity and threshold of ADH release has been advanced by the technological development of a sensitive radioimmunoassay. Evidence suggesting that ADH secretion is also mediated by nonosmotic stimuli involving a separate anatomic pathway from the hypothalamic osmoreceptor has been well documented. Experimental results suggest that the parasympathetic afferent pathways from both "high" and "low" pressure receptors constitute the most important nonosmotic pathways for ADH release. Factors such as hypoxia, altered hemodynamic states, alpha- and beta-adrenergic stimuli, nicotine, adrenal insufficiency, and advanced hypothyroidism are likely examples which activate this nonosmotic pathway. Clarification of the exact interrelationship between the osmotic and nonosmotic release of ADH needs further examination, particularly in the area of central neurotransmitters. However, available information allows for the proposal of a model of this interaction and its clinical implications which may explain many cases of "reset osmostat." Recent available data also provide support for ADH playing a role in the maintenance of blood pressure under certain circumstances. Like other potent vasoconstrictors, preliminary evidence suggests that ADH requires transcellular calcium influx for its vascular effects. Adrenal, thyroid, and edematous disorders have all been shown to be associated with abnormal water excretion. The results of recent studies indicate that these abnormal physiological states have impaired water excretion as a result of both nonosmolar factors stimulating ADH release and intrarenal factors, including diminished glomerular filtration rate or increased proximal tubule reabsorption which lead to decreased distal fluid delivery to the diluting segment of the nephron. Verney's original studies demonstrating the osmoreceptor regulation of ADH release remain a milestone in renal physiology. In the past decade, considerable new information about nonosmotic regulation of ADH has led to further understanding of renal water regulation in health and disease; nevertheless, many of these answers have only stimulated the imagination to ponder even more questions.
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PMID:The physiology of vasopressin release and the pathogenesis of impaired water excretion in adrenal, thyroid, and edematous disorders. 724 4

The action sites for parathyroid hormone (PTH), salmon calcitonin (SCT), and arginine-vasopressin (AVP) were investigated along the human nephron by measuring adenylate cyclase activity, using a single tubule in vitro microassay. Well-localized segments of tubule were isolated by microdissection from five human kidneys unsuitable for transplantation. PTH (10 IU/ml) increased adenylate cyclase activity in the convoluted and the straight proximal tubule, in the medullary and cortical portions of the thick ascending limb, and in the early portion of the distal convoluted tubule (corresponding stimulated:basal activity ratios were 64, 19, 10, 18, and 22, respectively). SCT (10 ng/ml) increased adenylate cyclase activity in the medullary and cortical portions of the thick ascending limb, in the early portion of the distal convoluted tubule, and, to a lesser extent, in the cortical and the medullay collecting tubule (activity ratios were 7, 14, 15, 3, and 3, respectively). AVP (1 microM) stimulated adenylate cyclase activity in the terminal nephron segments only, i.e., the late portion of the distal convoluted tubule, the cortical and medullary portions of the collecting tubule (activity ratios 81, 51, and 97, respectively). As measured in one experiment, nearly one-half maximal responses were obtained with 0.1 IU/ml PTH or 0.3 ng/ml SCT in thick ascending limbs and with 1 nM AVP in collecting tubules, suggesting that enzyme sensitivity to hormones as well preserved under the conditions used in this study.
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PMID:Adenylate cyclase responsiveness to hormones in various portions of the human nephron. 735 89

1. Iodinated vasopressin was microinjected into early proximal or distal tubules or Wistar and Brattleboro (diabetes insipidus) rats. Sites of infusion were determined by the lissamine green transit time method. 2. Urinary recovery of 125I after proximal and distal injections was 89 +/- SE 1.7% and 94 +/- 1.0% in Wistar rats (corrected for inulin) and 81 +/- 2.0 and 92 +/- 2.0% in Brattleboro rats (uncorrected); injection of hormone into vascular stars resulted in similar 125I recoveries from punctured and contralateral kidneys. 3. Radioactive substances excreted after perfusing proximal and distal sites in Brattleboro animals, and 125I-labelled hormone added to urine from the contralateral kidney, bound similarly to a specific arginine vasopressin antiserum and demonstrated similar radioactive elution profiles after passage through Sephadex G25 columns. 4. Incubation of labelled and unlabelled vasopressin with rat kidney homogenates resulted in similar and complete degradation of the hormone. 5. Results indicate that most of the vasopressin injected into either proximal or distal nephrons enters the urine intact, and no evidence of tubular secretion was found when perfusing vascular stars. Enzymes in rat renal tissue degrade labelled vasopressin, but the ability of the proximal tubule to hydrolyse the 125I-labelled vasopressin is limited, especially when compared with that reported for several linear peptide hormones.
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PMID:Fate of vasopressin perfused into nephrons of Wistar and Brattleboro (diabetes insipidus) rats. 735 33


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