Effect of calcitonin on urine concentration in the rat

1983 ◽  
Vol 244 (4) ◽  
pp. F432-F435 ◽  
Author(s):  
S. Carney ◽  
T. Morgan ◽  
C. Ray ◽  
L. Thompson
Keyword(s):  
Water Permeability ◽  
Partial Agonist ◽  
Collecting Duct ◽  
Free Water ◽  
Urine Concentration ◽  
Distal Nephron ◽  
Free Water Clearance ◽  
Normal Increase

Because mammalian distal nephron segments with both calcitonin- and antidiuretic hormone- (ADH) sensitive adenylate cyclase activity have been described, in vivo and in vitro experiments were performed to study the effect of calcitonin on rat distal nephron water permeability. Calcitonin 1 and 0.1 U/ml, but not 0.01 U/ml, significantly increased the diffusional water permeability in the isolated papillary collecting duct by 15 and 11%, respectively. However, this effect was small when compared with a 68% increase with a supramaximal concentration of ADH (from 4.0 +/- 0.3 to 6.7 +/- 0.9 microns/s; n = 6, P less than 0.01). The normal increase in water permeability with increasing concentration of ADH (0.02 and 0.2 mU/ml) was depressed by the previous addition of calcitonin (1 U/ml) to the bath but was unaltered with the supramaximal ADH concentration (2 mU/ml). Verapamil, a compound that antagonizes cellular calcium entry, did not alter the effect of calcitonin on diffusional water permeability. Calcitonin in concentrations of 0.05, 0.5, and 5 U/ml produced a significant reduction in urine flow and free water clearance. Pretreatment with calcitonin in these concentrations inhibited the antidiuretic action of ADH. These studies suggest that calcitonin acts as a partial agonist to ADH within the distal nephron. It is unclear whether such an action represents a physiological or a pharmacological effect.

Somatostatin as a Modulator of Distal Nephron Water Permeability

1993 ◽  
Vol 84 (4) ◽  
pp. 455-460 ◽  
Author(s):  
Cheryl Ray ◽  
Shane Carney ◽  
Trefor Morgan ◽  
Alastair Gillies
Keyword(s):  
Water Transport ◽  
Arginine Vasopressin ◽  
Water Permeability ◽  
Collecting Duct ◽  
Free Water ◽  
Distal Nephron ◽  
High Concentration ◽  
Free Water Clearance ◽  
Water Clearance

1. Experiments in vivo and in vitro were performed in the rat to define the role of somatostatin in modulating the hydro-osmotic action of arginine vasopressin. 2. Somatostatin had a biphasic effect on basal collecting duct diffusional water permeability with 10−9 mol/l somatostatin producing a 14% reduction in permeability, whereas concentrations of 10−6 and 10−5 mol/l significantly increased basal water permeability by 13% and 22%, respectively. Somatostatin (10−9 mol/l) also inhibited the increase in water permeability produced by arginine vasopressin, although this inhibitory effect was reduced by a 10-fold increase in arginine vasopressin concentration (5 ng/ml). 3. In the anaesthetized water-diuretic rat, low dose somatostatin (60 μg/h) increased free water clearance by 23% (P < 0.01), whereas increasing the somatostatin concentration (600 μg/h) produced a transitory 40% fall in free water clearance (P < 0.01). As in the experiment in vitro, somatostatin inhibited the action of arginine vasopressin, although a very high concentration of arginine vasopressin (250 ng/h) partly overcame this effect. 4. Glomerular filtration rate and renal electrolyte excretion (sodium, potassium, calcium, magnesium) were not altered by somatostatin, although renal inorganic phosphate excretion was increased. The papillary solute gradient was unaltered by somatostatin. 5. These results suggest that circulating somatostatin may have a physiological role in modulating distal nephron water transport with a low concentration directly inhibiting and a high concentration facilitating water transport. There is also evidence of competitive binding between somatostatin and arginine vasopressin which antagonizes the hydro-osmotic action of arginine vasopressin.

Tubular prostaglandin E2 production and its role in urinary hypotonicity after release of ureteral occlusion in the rat

1987 ◽  
Vol 73 (4) ◽  
pp. 395-399 ◽  
Author(s):  
Shozo Torikai
Keyword(s):  
Prostaglandin E2 ◽  
Collecting Duct ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Pge2 Production ◽  
Endogenous Prostaglandin ◽  
Collecting Ducts ◽  
Ureteral Occlusion

1. In order to explore the involvement of endogenous prostaglandin E2 (PGE2) in the urine concentration defect after ureteral occlusion, PGE2 production by isolated collecting ducts in vitro and effects of indomethacin on urine osmolality in vivo were examined. 2. Twenty-four hours ureter obstruction caused increased PGE2 production by the medullary collecting ducts, which was maintained at a high level on the day after release of obstruction (0.8 ± 0.2 pg/mm normal, 8.1 ± 0.9 pg/mm 24 h obstruction, and 6.6 ± 1.0 pg/mm post-obstruction, mean ± sem). An enhanced PGE2 production was also observed for papillary collecting duct on the day after release of 24 h ureteral occlusion (3.9 ± 0.5 pg/mm normal and 7.7 ± 1.2 pg/mm post-obstruction). 3. Administration of indomethacin to the unilateral post-obstructive rats slightly raised the urine osmolality of the post-obstructed kidney (from 339 ± 17 to 390 ± 22 mosmol/kg H2O), while it had a greater effect on the contralateral intact kidney (from 1569 ± 138 to 2567 ± 198 mosmol/kg H2O). 4. Our data may indicate that the urine concentration defect after 24 h ureteral occlusion is ascribable mainly to a mechanism other than increased endogenous PGE2.

PGE2 inhibits water permeability at a post-cAMP site in rat terminal inner medullary collecting duct

1992 ◽  
Vol 262 (2) ◽  
pp. F229-F235 ◽  
Author(s):  
S. P. Nadler ◽  
J. A. Zimpelmann ◽  
R. L. Hebert
Keyword(s):  
Water Permeability ◽  
Collecting Duct ◽  
Functional Expression ◽  
Intracellular Camp ◽  
Kinase C ◽  
Camp Analogue ◽  
Protein Kinase C Inhibitor ◽  
Medullary Collecting Duct

To assess sites and mechanism of action of prostaglandin E2 (PGE2) on water permeability (PF), we determined PGE2 effects on antidiuretic hormone (ADH)- and adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated PF in rat terminal inner medullary collecting ducts perfused in vitro. PGE2 (10(-7) M) reversibly inhibited ADH-stimulated PF (1.131 +/- 192 to 532 +/- 208 microns/s). In contrast to that observed in rabbit, PGE2 also inhibited an established PF response to the exogenous cAMP analogue 8-p-(chlorophenylthio)-cAMP (696 +/- 107 to 399 +/- 99 microns/s). PGE2 alone had no effect on PF. The protein kinase C inhibitor staurosporine (10(-8) M) blocked PGE2-mediated inhibition of cAMP-stimulated PF. PGE2 caused a rapid spikelike increase in intracellular calcium [( Ca2+]i) followed by a stable elevation above basal values. Only the latter effect was abolished in a zero calcium bath. Neither staurosporine nor cAMP altered the [Ca2+]i response. These studies are the first to demonstrate PGE2-mediated inhibition of an established PF response to cAMP independent of changes in intracellular cAMP. The pattern of [Ca2+]i release and sensitivity to staurosporine suggests that this effect is mediated via signaling through phospholipase C. The results underscore the importance of species differences, axial heterogeneity, and/or in vivo conditioning for functional expression of cellular signaling pathways.

Vasopressin regulation of inner medullary collecting ducts and compensatory changes in mice lacking adenosine A1 receptors

2008 ◽  
Vol 294 (3) ◽  
pp. F638-F644 ◽  
Author(s):  
Timo Rieg ◽  
Kanishka Pothula ◽  
Jana Schroth ◽  
Joseph Satriano ◽  
Hartmut Osswald ◽  
...  
Keyword(s):  
Arginine Vasopressin ◽  
Free Water ◽  
Urinary Flow ◽  
Free Water Clearance ◽  
Water Excretion ◽  
Water Loading ◽  
Collecting Ducts ◽  
Camp Formation

Activation of adenosine A1 receptors (A1R) can inhibit arginine vasopressin (AVP)-induced cAMP formation in isolated cortical and medullary collecting ducts. To assess the in vivo consequences of the absence of A1R, we performed experiments in mice lacking A1R (A1R−/−). We assessed the effects of the vasopressin V2 receptor (V2R) agonist 1-desamino-8-d-arginine vasopressin (dDAVP) on cAMP formation in isolated inner medullary collecting ducts (IMCD) and on water excretion in conscious water-loaded mice. dDAVP-induced cAMP formation in isolated IMCD was significantly greater (∼2-fold) in A1R−/− compared with wild-type mice (WT) and, in contrast to WT, was not inhibited by the A1R agonist N6-cyclohexyladenosine. A1R−/− and WT had similar basal urinary excretion of vasopressin, expression of aquaporin-2 protein in renal cortex and medulla, and acute increases in urinary flow rate and electrolyte-free water clearance in response to the V2R antagonist SR121463 or acute water loading; the latter increased inner medullary A1R expression in WT. Dose dependence of dDAVP-induced antidiuresis after acute water loading was not different between the genotypes. However, A1R−/− had greater inner medullary expression of cyclooxygenase-1 under basal conditions and of the P2Y2 and EP3 receptor in response to water loading compared with WT mice. Thus vasopressin-induced cAMP formation is enhanced in isolated IMCD of mice lacking A1R, but the adenosine-A1R/V2R interaction demonstrated in vitro is likely compensated in vivo by multiple mechanisms, a number of which can be “uncovered” by water loading.

scholarly journals Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration

2010 ◽  
Vol 299 (3) ◽  
pp. F577-F584 ◽  
Author(s):  
Weidong Wang ◽  
Chunling Li ◽  
Sandra Summer ◽  
Sandor Falk ◽  
Robert W. Schrier
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
Receptor Activation ◽  
Urine Concentration ◽  
At1 Receptor ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Vitro Effect

The study was undertaken to examine the potential cross talk between vasopressin and angiotensin II (ANG II) intracellular signaling pathways. We investigated in vivo and in vitro whether vasopressin-induced water reabsorption could be attenuated by ANG II AT1 receptor blockade (losartan). On a low-sodium diet (0.5 meq/day) dDAVP-treated animals with or without losartan exhibited comparable renal function [creatinine clearance 1.2 ± 0.1 in dDAVP+losartan (LSDL) vs. 1.1 ± 0.1 ml·100 g−1·day−1 in dDAVP alone (LSD), P > 0.05] and renal blood flow (6.3 ± 0.5 in LSDL vs. 6.8 ± 0.5 ml/min in LSD, P > 0.05). The urine output, however, was significantly increased in LSDL (2.5 ± 0.2 vs. 1.8 ± 0.2 ml·100 g−1·day−1, P < 0.05) in association with decreased urine osmolality (2,600 ± 83 vs. 3,256 ± 110 mosmol/kgH2O, P < 0.001) compared with rats in LSD. Immunoblotting revealed significantly decreased expression of medullary AQP2 (146 ± 6 vs. 176 ± 10% in LSD, P < 0.01), p-AQP2 (177 ± 13 vs. 214 ± 12% in LSD, P < 0.05), and AQP3 (134 ± 14 vs. 177 ± 11% in LSD, P < 0.05) in LSDL compared with LSD. The expressions of AQP1, the α1- and γ-subunits of Na-K-ATPase, and the Na-K-2Cl cotransporter were not different among groups. In vitro studies showed that ANG II or dDAVP treatment was associated with increased AQP2 expression and cAMP levels, which were potentiated by cotreatment with ANG II and dDAVP and were inhibited by AT1 blockade. In conclusion, ANG II AT1 receptor blockade in dDAVP-treated rats on a low-salt diet was associated with decreased urine concentration and decreased inner medullary AQP2, p-AQP2, and AQP3 expression, suggesting that AT1 receptor activation plays a significant role in regulating aquaporin expression and modulating urine concentration in vivo. Studies in collecting duct cells were confirmatory.

Abstract 069: β-Catenin Signaling Contributes to Angiotensin II-Induced Hypertension via Activation of Sodium Transporters in the Distal Nephron

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Xiaohan Lu ◽  
Kexin Peng ◽  
Fei Wang ◽  
Tianxin Yang
Keyword(s):  
Protein Expression ◽  
Collecting Duct ◽  
Urine Volume ◽  
Fold Increase ◽  
Control Group ◽  
Protein Abundance ◽  
Distal Nephron ◽  
Induced Hypertension

β-Catenin signaling plays an important role in regulation of development as well as tissue homeostasis. Recently, we have shown that this pathway is involved in regulation of collecting duct (CD) function. Here, we examined the role of β-catenin signaling in AngII-induced hypertension. C57/BL6 mice were administered for 7 d with vehicle, AngII alone (300 ng/kg/min) or in combination with an inhibitor of β-catenin pathway, ICG-001 (50 mg/kg/d) both via an osmotic mini-pump. Radiotelemetry demonstrated that ICG-001 effectively attenuated AngII-induced hypertension (MAP on day 7: 112.5 ± 2.02 in Control group vs. 137±2.07 in AngII group vs. 119.2±2.26 mmHg in AngII/ICG-001 group, n = 7-9, p<0.05) accompanied with a 34% (34 of 100) increase in 24-h urine volume and a 35% (35 of 100) increase in 24-h urinary Na+ excretion. Following AngII treatment, urinary renin activity and renin content both exhibited a more than 10-fold increase which was completely blocked by ICG-001. AngII infusion selectively elevated α-ENaC protein abundance in the renal medulla but not in the renal cortex; the renal medullary upregulation of α-ENaC protein expression was attenuated by ICG-001. Similarly, renal cortical NCC and NKCC2 protein expression was elevated by AngII infusion; this upregulation of NCC and NKCC2 protein expression was again abolished by ICG-001. In contrast, NHE3 protein abundance remained constant. In cultured mpkCCD cells transfected with a β-catenin-driven luciferase construct, AngII treatment at 500 nM for 24 h induced a 10-fold increase in the reporter activity which was sensitive to ICG-001 (1 μM). In these cells, the AngII treatment induced amiloride-sensitive Na + transport as assessed by epithelial volt-ohmmeter, which was completely blocked by ICG-001. Protein expression of α-ENaC exhibited the similar pattern of changes as ENaC activity whereas the expression of β- or γ-ENaC remained constant. ICG-001 was not associated with noticeable toxicity in vivo or in vitro. In summary, these results suggest that β-catenin signaling mediates AngII-induced hypertension at least in part through regulation of intrarenal renin response and the expression of Na+ transporters in the distal nephron.

Acute Effect of Parathyroid Hormone on Urine Concentration in the Rat

1995 ◽  
Vol 88 (2) ◽  
pp. 197-201 ◽  
Author(s):  
S. L. Carney ◽  
A. H. B. Gillies
Keyword(s):  
Parathyroid Hormone ◽  
Arginine Vasopressin ◽  
Partial Agonist ◽  
Acute Effect ◽  
Inhibitory Effect ◽  
Urine Concentration ◽  
Antidiuretic Effect ◽  
Plasma Calcium Concentration ◽  
Subsequent Effect

1. It has been demonstrated that parathyroid hormone can increase adenylate cyclase activity in the rat papilla, produce a small antidiuretic effect and in vitro can interfere with the action of arginine vasopressin on water transport. Clearance studies were performed in the anaesthetized water diuretic thyroparathyroidectomized rat to evaluate further the effect of parathyroid hormone on urine concentration in the presence and absence of arginine vasopressin. 2. A maximal phosphaturic concentration of rat parathyroid hormone (2 μg/kg) reduced urine flow from 125 ± 7 to 81 ± 9 μl/min within 10 min (P < 0.01). Addition of a maximal antidiuretic concentration of arginine vasopressin (100 ng/kg) produced a delayed and diminished antidiuretic response when compared with a group of rats not pretreated with parathyroid hormone (47 ± 5 compared with 27 ± 5 μl/min; P < 0.01). However, a supramaximal arginine vasopressin concentration (1000 ng/kg) produced a maximal antidiuretic effect in the presence of parathyroid hormone. 3. To evaluate further the inhibitory effect of parathyroid hormone on arginine vasopressin-induced anti-diuresis, parathyroid hormone (2 μg/kg) was administered to one group of rats and a minimally effective arginine vasopressin concentration (7.5 ng/kg) to another group, which produced a similar antidiuretic effect. However, the subsequent effect of a maximal antidiuretic arginine vasopressin concentration (100 ng/kg) was again significantly blunted in the group pretreated with parathyroid hormone. 4. Parathyroid hormone produced only a small increase in mean plasma calcium concentration, and glomerular filtration rate was not altered by either hormone. 5. These results demonstrate that high physiological concentrations of parathyroid hormone do have a significant antidiuretic effect and can interfere with the action of arginine vasopressin. This suggests that parathyroid hormone may act as a partial agonist to arginine vasopressin in the collecting system.

Is the function of the renal papilla coupled exclusively to an anaerobic pattern of metabolism?

1979 ◽  
Vol 236 (5) ◽  
pp. F423-F433 ◽  
Author(s):  
J. J. Cohen
Keyword(s):  
Oxidative Metabolism ◽  
Aerobic Glycolysis ◽  
Collecting Duct ◽  
High Rate ◽  
O2 Uptake ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Mitochondrial Oxidative Metabolism

It is widely accepted that in vivo the function of the papilla of the mammalian kidney is supported primarily by anaerobic metabolism. As a result, the major source of energy for support of function in the papilla is considered to be derived from glycolysis. This orientation originates from two concepts: 1) that in vivo the gaseous environment of the papilla has such a low PO2 that O2 availability limits O2 consumption, and 2) that papillary tissue has a high rate of glycolysis when compared with either cortical tissue or extrarenal tissues. It has also been tacitly assumed that papillary tissue has a "low" O2 uptake. Review of the measurements of PO2 of papillary tissue and of urine PO2 indicates that the PO2 of papillary tissue should not limit its aerobic mitochondrial oxidative metabolism. While the rate of aerobic glycolysis in papillary tissue is high, simultaneously papillary tissue has a rate of O2 uptake similar to that of liver and higher than that of muscle. The major (two-thirds) source of energy for papillary tissue in vitro is from O2 uptake. That papillary tissue is not exclusively dependent on glucose for its energy requirements is indicated by the greater stimulation of papillary tissue QO2 by succinate than by glucose. Thus, papillary tissue has both a high aerobic mitochondrial oxidative metabolism and a high aerobic glycolytic metabolism. It is suggested that the mechanism for the high rate of aerobic glycolysis in the presence of an adequate O2 supply is due to the relatively small mass of mitochondria in papillary tissue in relation to the amount of work done by the tissue. As a result of the limited rate of ATP production by the mitochondrial electron transport chain, the phosphorylation state ([ATP]/[ADP][Pi]) is reduced and the cytoplasmic redox state ([NAD+]/[NADH]) of the papillary collecting duct cells also becomes more reduced; changes in both ratios enhance the rate of glycolysis. This limited metabolic capacity of the collecting duct cells may permit an excess volume of solute and water to be excreted during volume expansion diuresis. The metabolic characteristics of the papilla, when compared to cortex, also provide a basis for the observed differences in substrate selectivity of cortex and medulla with respect to utilization of glucose and lactate. The experimental approaches that may provide information bearing on the suggested mechanisms for regulation of papillary metabolism in relation to tubular work functions are indicated.

scholarly journals Collecting Duct Is a Site of Sodium Retention in PAN Nephrosis: A Rationale for Amiloride Therapy

2001 ◽  
Vol 12 (3) ◽  
pp. 598-601 ◽  
Author(s):  
GEORGES DESCHÊNES ◽  
MONIKA WITTNER ◽  
ANTONIO DI STEFANO ◽  
SYLVIE JOUNIER ◽  
ALAIN DOUCET
Keyword(s):  
Collecting Duct ◽  
Urinary Sodium Excretion ◽  
Sodium Balance ◽  
Sodium Reabsorption ◽  
Puromycin Aminonucleoside ◽  
Aldosterone Receptor ◽  
Collecting Tubules ◽  
A Site

Abstract. Micropuncture studies of the distal nephron and measurements of Na,K-ATPase activity in microdissected collecting tubules have suggested that renal retention of sodium in puromycin aminonucleoside (PAN) nephrotic rats originates in the collecting duct. The present study demonstrated this hypothesis by in vitro microperfusion and showed that amiloride was able to restore sodium balance. Indeed, isolated perfused cortical collecting ducts from PAN-treated rats exhibited an abnormally high transepithelial sodium reabsorption that was abolished by amiloride, and in vivo administration of amiloride fully prevented decreased urinary sodium excretion and positive sodium balance in nephrotic rats. As expected from the aldosterone independence of Na+ retention in PAN nephrotic rats, blockade of aldosterone receptor by potassium canrenoate did not alter urinary Na+ excretion, Na+ balance, or ascites formation in PAN nephrotic rats.

Sign in / Sign up

Export Citation Format

Share Document