Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because the rat papilla has parathyroid hormone (PTH)-sensitive adenylate cyclase and because of indirect evidence that PTH may alter collecting duct water and also calcium transport, the effects of PTH on rat papillary collecting duct water and calcium transport have been studied. PTH in concentrations of 50 and 500 ng/ml significantly increased diffusional water permeability by 20 and 38%, respectively, while 5,000 ng/ml had no additional effect. This permeability response was small when compared to a 78% increase in water permeability with a maximal (0.5 ng/ml) concentration of antidiuretic hormone (ADH). The normal increase in water permeability with ADH was depressed in the presence of PTH (500 ng/ml) but was overcome when the ADH concentration was increased from 0.5 to 5 ng/ml. Neither PTH nor ADH altered the permeability of the collecting duct to calcium which was low (0.19 +/- 0.03 micron/s). Increasing either the bath or perfusate calcium concentration from 1 to 5 mM did not alter calcium permeability. These studies suggest that PTH acts as a partial agonist to ADH within the papillary collecting duct and that PTH is unlikely to have a major role in collecting duct calcium transport.
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PMID:Effect of parathyroid and antidiuretic hormone on water and calcium permeability in the rat collecting duct. 338 69

Clearance experiments were performed to characterize the sensitivity to vasopressin of the thick ascending limbs and collecting duct system of the rat kidney. The response of the thick ascending limbs was evaluated by measuring the Mg2+ excretion rate in the urine, since the [arginine-8] vasopressin-mediated effects on Mg2+ excretion are the direct result of a stimulation of Mg2+ reabsorption in this nephron segment, and the response of the collecting ducts was evaluated by changes in urine flow. To avoid the effects of parathyroid hormone, glucagon, and calcitonin, which stimulate Mg2+ reabsorption in the thick ascending limb and distal tubule, and of calcitonin, which increases the permeability of the cortical collecting ducts to water, experiments were performed on Brattleboro D. I. rats (with hereditary diabetes insipidus, due to a lack of [Arg8]vasopressin) acutely deprived of endogenous parathyroid hormone, calcitonin, and glucagon. Vasopressin infused at rates up to 5 pg/min did not reduce the Mg2+ fractional excretion rate, whereas at 5 pg/min water excretion was decreased by 50%. The half-maximal reduction of Mg2+ excretion occurred at vasopressin infusion rates 4-6 times higher than those necessary to diminish the water excretion rate to the same extent. We conclude that in vivo, two segments involved in the production of concentrated urine have different sensitivities to vasopressin and that this difference in sensitivity is very similar for the biological response in vivo and the adenylate cyclase activation in vitro. We suggest that both the magnitude and the nature of the effects of [Arg8]vasopressin on the kidney may vary according to the required antidiuretic response.
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PMID:Sensitivities of rat kidney thick ascending limbs and collecting ducts to vasopressin in vivo. 345 86

One of the most common and serious side effects of diuretic therapy is in increased urinary loss of K. Another, although less well publicized, side effect of diuretic therapy is excessive urinary loss of Mg. In examining the effects of diuretics on Mg and K metabolism, the following factors should be taken into account: site of action and duration of action of diuretics, duration of treatment and dosage used, concurrent drug therapy, underlying disease conditions and dietary intake of Mg. Diuretics acting in the proximal tubule tend to have only minor effects on Mg excretion. Loop-blocking diuretics, however, cause major urinary losses of Mg. The Mg-wasting effects of loop-blocking diuretics have been demonstrated in large numbers of experimental and clinical studies, and the findings are consistent with micropuncture studies in laboratory animals which indicate the loop of Henle as the major site of Mg reabsorption. The effects of thiazide diuretics on Mg excretion are less well established than those of loop-blocking diuretics. Experimental studies demonstrate that thiazides have little or no direct effect on Mg transport in the nephron. However, some clinical studies indicate that thiazide treatment may induce Mg loss. This may be secondary to alterations in the renin-angiotensin-aldosterone system and in the calcium and parathyroid hormone and may be contributed to by concurrent drug treatment and the underlying disease conditions. K-sparing diuretics are usually administered concomitantly with more potent diuretics to counteract diuretic-induced K depletion. These agents act in the late distal tubule and collecting duct. Evidence has accumulated in recent years indicating that these drugs may also exert some Mg-sparing properties. Experimental and clinical investigations from our own laboratories and from other investigators will be reviewed. In animal studies, a dose-response relationship has been established for the actions of amiloride in reducing fractional excretion of Mg and K during furosemide-induced diuresis. The effects of amiloride on Mg excretion are less than those on K excretion, and this is compatible with the different handling of K and Mg in the distal tubule and collecting duct. The effects of aldosterone antagonists on Mg excretion are less well established than those of amiloride. Some recent studies indicate that converting-enzyme inhibitors may also influence Mg and K metabolism. The Mg-sparing actions of drugs may have important therapeutic implications.
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PMID:Magnesium and potassium-sparing diuretics. 354 14

The aging kidney suffers reduction both in mass and in glomerular filtration rate. These changes may be totally or partially due to atherosclerosis and hypertension, which reduce renal blood flow. Superimposed on these processes, and perhaps responsible for primary loss of renal mass irrespective of renal vascular disease, is glomerular damage and involution that is a consequence of adaptive increases in glomerular perfusion pressure that occurs as the number of nephrons decline with age. The data available at this time do not allow us to distinguish between these two potential mechanisms of renal senescence. The decline in GFR is in turn responsible for reduced renal acidification and the reduced renal clearance of drugs that are normally removed by the kidney. Certain renal functions, however, are depressed to a greater extent than is GFR. Both the ability to maximally dilute the urine and to maximally concentrate it are controlled by serum ADH concentrations and by the action of that hormone on the collecting duct. Aged rats do not maximally secrete ADH under conditions of dehydration and the effect of ADH on the kidney is also attenuated. Elderly humans also cannot maximally suppress ADH secretion when serum osmolality is reduced. Likewise, the renin-angiotensin-aldosterone axis is poorly responsive to volume depletion in aging subjects. As a result, elderly individuals cannot maximally retain sodium under conditions of plasma volume contraction out of proportion to reduction in GFR. The kidney is the site of vitamin D1 hydroxylation. Hydroxylation of vitamin D is reduced out of proportion to any reduction in GFR in the rat. There are no data as yet available on the effect of aging and the production of erythropoietin, a principal regulator of red blood cell mass. Neither are there data available on changes that might occur with advancing age in the ability of the aging kidney to metabolize various hormones, such as parathyroid hormone, glucagon, and insulin. The mechanisms and the full biochemical and physiologic consequences of renal senescence remain to be fully elucidated.
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PMID:The aging kidney. 391

The papillary collecting duct (PCD) is considered to be of major importance in the final elaboration of the urine, but the metabolism of cyclic adenosine 3',5'-monophosphate (cAMP) has not yet been directly studied in the PCD. Therefore, in the present study we examined the basic properties of the cAMP system in isolated PCD microdissected from rat kidney. Vasopressin (VP) caused a marked (5- to 10-fold) stimulation of adenylate cyclase (AdC) but parathyroid hormone, calcitonin, isoproterenol, and bradykinin were without effect. A gradual increase in osmolality from 200 mosM had a biphasic effect on AdC, first enhancing (at 800 mosM) then inhibiting AdC activity at 2,000 mosM. cAMP-phosphodiesterase activity was inhibited as osmolality was increased from 200 to 800 mosM and the inhibition remained constant to 2,000 mosM. Incubation of intact PCD with VP resulted in a threefold increase in cAMP levels. As the osmolality of the incubation medium ws increased from 300 to 2,000 mosM, both basal and VP-stimulated cAMP levels continued to increase. Prostaglandin E2 (PGE2) (10(-5) M) alone (in the absence of vP) caused an increase in AdC activity, but the same dose of PGE2 had no effect on AdC activity stimulated by submaximal or maximal doses of VP. PGE2 (10(-5) M) caused a small increase in cAMP levels in intact PCD. On the other hand, PGE2 inhibited VP-stimulated cAMP levels by 50%. Incubation of PCD with PGE2 had no effect on cAMP-phosphodiesterase activity. The results demonstrate that osmolality in the physiologic range has a major influence on cAMP metabolism in the PCD and document an antagonism between PGE2 and VP at the level of cAMP accumulation in the PCD.
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PMID:ADH-sensitive cAMP system in papillary collecting duct: effect of osmolality and PGE2. 626 88

The effect of the absence of parathyroid hormone on nephron acidification was determined in rats after acute thyroparathyroidectomy (TPTX). Tubular fluid samples were obtained from the superficial late proximal tubule (LPT), the early distal tubule ( EDT ), and along the inner medullary collecting duct (IMCD), and the results were compared with those obtained from control rats. In the LPT after TPTX, pH was lower, 6.66 +/- 0.01 vs. 6.73 +/- 0.01, and ammonium and net acid delivery were increased significantly. In the EDT no differences in pH, bicarbonate, or net acid were found between groups, whereas ammonium and acid phosphate were significantly different. Along the IMCD in control rats, pH decreased from 6.58 to 5.21 and the addition of about 430 nmol/min of net acid was observed. After TPTX more net acid entered the duct and pH was lower, 5.66, but did not change; neither did the amount of bicarbonate, ammonium, acid phosphate, or net acid change significantly along the duct. Net acid excretion was not different, however, among groups. These results demonstrate that TPTX markedly affects nephron acidification, increasing net acid along the proximal tubule. In contrast to that in control rats, however, net acidification is completed prior to the IMCD. We conclude that the acute absence of parathyroid hormone may significantly affect local nephron acidification but does not alter acid excretion.
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PMID:Effect of acute thyroparathyroidectomy on nephron acidification. 672 Sep 62

The mode and mechanism of phosphate transport in the light portion of the rabbit cortical collecting duct were studied with isolated tubular perfusion. Control studies (n = 48) revealed a mean transepithelial potential difference (PD) of -16.5 +/- 1.3 mV and net phosphate absorption (JPO4) of 0.58 +/- 0.07 pmol.mm-1.min-1. To characterize transport, the effects of flow rate, ouabain, amiloride, and phosphate concentration, and parathyroid hormone (PTH) were analyzed. There was a significant linear relationship between JPO4 and flow rate (n = 48) (r = 0.71, P less than 0.025). Increasing the difference between lumen and bath phosphate concentration from -8.0 to +8.0 mg/dl was associated with a stepwise increase in JPO4 from -0.18 +/- 0.02 to 0.93 +/- 0.05 pmol.mm-1.min-1. PTH had no effect on JPO4. To assess the effects of PD, the tubules were treated with either amiloride (n = 6) or ouabain (n = 7). JPO4 fell significant in both circumstances with reduction of PD, although there remained significant residual transport following amiloride addition. The data demonstrate significant phosphate transport in this segment that is independent of PTH and altered by transepithelial electrical and concentration gradients as well as flow rate.
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PMID:Phosphate transport in the light segment of the rabbit cortical collecting tubule. 706 47

We recently reported a novel intracellular mechanism of Na-K-adenosinetriphosphatase (Na-K-ATPase) regulation in the cortical collecting duct (CCD) by agents that increase cell adenosine 3',5'-cyclic monophosphate (cAMP), which involves stimulation of protein kinase A (PKA) and phospholipase A2 (PLA2). We now determined whether this mechanism also operates in other nephron segments. In the medullary thick ascending limb (MTAL) dopamine, the DA1 agonist fenoldopam, forskolin, or dibutyryl-cAMP inhibited Na-K-ATPase activity, similar to results in CCD. In both segments this effect was blocked by 20-residue inhibitory peptide (IP20), a peptide inhibitor of PKA, but not by staurosporine, a protein kinase C (PKC) inhibitor. PKC activators phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate, and 1,2-myristate 13-acetate, phorbol 12,13-dibutyrate, and 1,2-dioctanoylglycerol had no effect on Na-K pump activity in either CCD or MTAL. In contrast, all three PKC activators inhibited pump activity in the proximal convoluted tubule (PCT), an effect reproduced only by dopamine or by parathyroid hormone [PTH-(1-34)]. In PCT the pump inhibition by dopamine or PTH-(1-34) was abolished by staurosporine but not by IP20. The PLA2 inhibitor mepacrine prevented the effect of all agents, and arachidonic acid produced a dose-dependent pump inhibition in each of the three segments studied. We conclude that intracellular mechanisms of Na-K-ATPase regulation differ along the nephron, as they involve activation of PKA in CCD and MTAL and of PKC in PCT. These two pathways probably share a common mechanism in stimulating PLA2, arachidonic acid release, and production of eicosanoids in both the proximal and distal nephron.
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PMID:Different mechanisms of renal Na-K-ATPase regulation by protein kinases in proximal and distal nephron. 821 99

While many studies have demonstrated a nephrogenic diabetes insipidus syndrome (NDI) with prolonged lithium (Li) treatment, experiments in the isolated rat papillary collecting duct have suggested that the defect may be due to a circulating factor that inhibits the action of arginine vasopressin (AVP). Since Li-treatment can produce a form of hyperparathyroidism and parathyroid hormone (PTH) can act as a partial agonist to AVP, in vivo and in vitro studies were performed on rats made polyuric by daily intraperitoneal (i.p.) Li (4 mmol/kg) treatment. Li-treatment for three weeks produced an increase in PTH (194 +/- 20 compared with 118 +/- 18 pg/ml in control rats; P < 0.01) as well as an increase in the plasma calcium concentration (2.38 +/- 0.05 compared with 2.25 +/- 0.04 mmol/liter; P < 0.05). Clearance studies were performed on water loaded Li-treated and control rats, and the defect in urine concentration was only observed with a low physiological concentration of AVP (10 mU/kg body wt over 5 min). Maximal urine osmolality was 328 +/- 31 compared with 613 +/- 81 mOsm/kg (P < 0.05) in controls. There was no detectable difference with a prolonged maximal physiological AVP concentration (10 mU bolus and 50 mU/kg body wt per hr) and papillary solute concentrations were unchanged. When Li-treated rats had been parathyroidectomized (PTX), a significant difference in urine concentration with the low AVP concentration could not be demonstrated when compared to non-PTX control rats. In the isolated papillary collecting duct preparation a medium was used that contained fresh plasma from Li-treated or control rats, both intact and PTX. Experiments using plasma from Li-treated intact rats produced only a 25.4 +/- 5.1% increase in diffusional water permeability with the addition of AVP (200 microU/ml) compared to 52.6 +/- 9.0% in control rats (P < 0.01). However, when plasma from Li-treated PTX rats was used, the AVP induced increase in water permeability (54.7 +/- 11.2%) was not significantly different from that observed in PTX control rats. These studies show that the NDI-like defect in Li-treatment is small and easily overcome by higher concentrations of AVP and suggests that the concentration defect is at least in part due to increased circulating levels of PTH acting as a partial agonist to AVP and thereby inhibiting its hydroosmotic action.
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PMID:Mechanism of lithium-induced polyuria in the rat. 884 Feb 63

We recently cloned extracellular Ca(2+)-sensing receptors (CaRs) from bovine parathyroid and rat kidney that play key roles in Ca2+ homeostasis. Inactivating mutations of the CaR in the inherited human disorder, familial hypocalciuric hypercalcemia, cause reduced responsiveness of the parathyroid to extracellular Ca2+ (Cao2+), as well as abnormally avid renal tubular reabsorption of both Ca2+ and Mg2+ in the distal tubule, suggesting an important role for the CaR in regulating parathyroid hormone (PTH) secretion and renal handling of divalent cations. High Cao2+ also inhibits vasopressinstimulated adenosine 3',5'-cyclic monophosphate accumulation in the medullary thick ascending limb (MTAL) and water reabsorption in the collecting duct (CD) and modulates various other aspects of renal function. The relevance of the CaR to these processes, however, is uncertain. Reduced responsiveness of vasopressin-and PTH-mediated actions on the kidney have been described in the newborn that could potentially reflect effects of the CaR on these aspects of renal function. To define further the role of the CaR in regulating renal function, including the above-mentioned changes during the perinatal period, therefore, we have studied its ontogeny in rat kidney. Northern and Western blot analyses, as well as immunohistochemistry with CaR-specific probes, demonstrate that there is little prenatal expression of the extracellular Ca(2+)-sensing receptor, except in large tubules and branching ureteric buds of developing nephrons. Postnatally, CaR mRNA and protein increase markedly during the 1st wk, related principally to expression of the receptor in the developing TAL and, to a lesser extent, in the CD. The level of expression of the receptor remains nearly constant after postnatal day 14. These results demonstrate that the perinatal increases in expression of CaR mRNA and protein parallel its tissue-specific renal expression. Furthermore, it is possible that some of the previously described changes in renal handling of divalent cations and water in the perinatal and immediate postnatal period are related, in part, to the increasing levels of expression of the CaR and resultant inhibitory effects on the actions of PTH and antidiuretic hormone on the developing nephron.
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PMID:Ontogeny of the extracellular calcium-sensing receptor in rat kidney. 885 37


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