Inhibition of vasopressin action by vanadate in the cortical collecting tubule

1983 ◽  
Vol 245 (6) ◽  
pp. F772-F777
Author(s):  
R. M. Edwards ◽  
J. J. Grantham
Keyword(s):  
Water Permeability ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Luminal Membrane ◽  
Collecting Tubule ◽  
Transepithelial Voltage ◽  
Collecting Tubules ◽  
A Site ◽  
Atpase Inhibition ◽  
Camp Formation

The effect of vanadate, a potent inhibitor of Na-K-ATPase, on the hydroosmotic response to vasopressin (AVP) and transepithelial voltage (Vt) in cortical collecting tubules was examined. At 37 degrees C, exposure of collecting tubules to bath vanadate (10(-4) M) for 30 min inhibited the increase in hydraulic water permeability (Lp) in response to AVP or 8-bromo-cyclic adenosine monophosphate by 68 and 76%, respectively. When vanadate was present only in the lumen no inhibition of the AVP response was observed. Incubation of tubules with ouabain (10(-5) M) for 30 min inhibited the AVP-induced increase in Lp to the same extent as vanadate. At 25 degrees C, vanadate inhibited the increase in Lp by AVP if added before but not after the hormone. Addition of vanadate to the bath caused a rapid decrease in the lumen-negative Vt that is consistent with Na-K-ATPase inhibition. Luminal vanadate also inhibited Vt but the rate of decrease of Vt was much slower than in the presence of bath vanadate. We conclude that vanadate inhibits the development but not the maintenance of the AVP-induced increase in water permeability in the collecting tubule. Since the effect of ouabain was similar to that of vanadate, the results suggest that inhibition of Na-K-ATPase directly or indirectly interferes with the initiation of the AVP-induced increase in luminal membrane water permeability at a site distal to cAMP formation.

Hydroosmotic response of collecting tubules to ADH or cAMP at reduced peritubular sodium

1982 ◽  
Vol 243 (5) ◽  
pp. F503-F513 ◽  
Author(s):  
G. Frindt ◽  
E. E. Windhager ◽  
A. Taylor
Keyword(s):  
Water Permeability ◽  
Exchange Process ◽  
Adenosine Monophosphate ◽  
Ringer Solution ◽  
Ion Activity ◽  
Amphibian Urinary Bladder ◽  
Collecting Tubule ◽  
Nephron Segment ◽  
Collecting Tubules ◽  
Cortical Collecting Tubule

Changes in cytosolic Ca2+ activity have been implicated in the hydroosmotic response to vasopressin (VP) in amphibian urinary bladder; the level of cytosolic free Ca2+ may be regulated, in part, by a process of Na-Ca exchange across the basolateral cell membrane. To assess whether similar mechanisms operate in the mammalian nephron, the effect of low peritubular [NA] on the hydraulic conductivity (Lp) of the isolated perfused rabbit collecting tubule (CT) exposed to either 20 microunits/ml VP or 5 X 10(-5) M 8-[p-chlorophenylthio]-cyclic 3',5'-adenosine monophosphate (ClPheS-cAMP) was studied. Low peritubular [Na] had no effect on the basal water permeability of the CT. After exposure to VP, CTs bathed in 145 mM Na Ringer solution developed an Lp of 324 +/- 27 X 10(-7) cm.s-1.atm-1, while tubules bathed in 4 mM Na and 141 mM tetramethylammonium Ringer solution achieved an Lp of only 112 +/- 13 X 10(-7) cm.s-1.atm-1 (P less than 0.001). Inhibition of the VP response was estimated to be half-maximal when peritubular Na was 120 mM. The hydroosmotic response to ClPheS-cAMP was diminished by 44% of the control values when CTs were bathed in a 4 mM Na medium; this inhibition was greatly attenuated when the peritubular Ca concentration was reduced to 0.05 mM. These results are consistent with the view that 1) a Na-Ca exchange process operates at the basolateral surface of the mammalian cortical collecting tubule cells, and 2) elevated cytosolic Ca ion activity inhibits the increase in water permeability elicited by VP or cAMP in this nephron segment.

Mechanisms of lithium-vasopressin interaction in rabbit cortical collecting tubule

1987 ◽  
Vol 252 (6) ◽  
pp. F1080-F1087 ◽  
Author(s):  
E. Cogan ◽  
M. Svoboda ◽  
M. Abramow
Keyword(s):  
Water Permeability ◽  
Regulatory Protein ◽  
Competitive Inhibitor ◽  
Inhibitory Effect ◽  
Regulatory Proteins ◽  
Collecting Tubule ◽  
Bordetella Pertussis Toxin ◽  
Guanine Nucleotide Regulatory Protein ◽  
Collecting Tubules ◽  
Stimulation Of

In single cortical collecting tubules (CCT) of the rabbit, guanosine 5'-triphosphate (GTP) increased the arginine vasopressin (AVP)-stimulated adenylate cyclase (AC) by 60% (P less than 0.05). In contrast, guanosine 5' O-(2-thio)-diphosphate (GDP-beta S), a competitive inhibitor of GTP action on the stimulatory guanine regulatory protein (Ns), reduced the AVP-stimulated AC activity by 72% (P less than 0.001), indicating the presence of endogenous GTP in the cells under study. That inhibitory effect was reversed by the addition of GTP to the incubation medium. In isolated perfused CCT, cholera toxin (CT) induced a significant increase in water permeability in the absence of AVP. In contrast, Bordetella pertussis toxin (BPT) did not modify the low AVP-independent water permeability. Lithium, an inhibitor of the hydrosmotic action of AVP, also inhibits the hydrosmotic action of CT by 70% (P less than 0.05) but not that of forskolin. The conclusions of the present study are Ns is required for AVP stimulation of AC in the CCT; Ns is functionally active in this system as evidenced by the hydrosmotic effect of CT; the lack of effect of BPT suggests that the low AVP-independent water permeability in the CCT is not the result of a tonic inhibition of the AC operating through the inhibitory guanine nucleotide regulatory protein; and the inhibition by lithium of the hydrosmotic action of AVP in the CCT appears to involve an interaction with the regulatory proteins (probably Ns) or with their binding to the catalytic unit of AC.

Protein kinase C activation and positive and negative agonist regulation of 3′, 5′-cyclic adenosine monophosphate levels in cultured rat Sertoli cells

1993 ◽  
Vol 128 (6) ◽  
pp. 568-572 ◽  
Author(s):  
Lars Eikvar ◽  
Kristin Austlid Taskén ◽  
Winnie Eskild ◽  
Vidar Hansson
Keyword(s):  
Sertoli Cells ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Dependent Manner ◽  
Camp Production ◽  
Camp Phosphodiesterase ◽  
Concentration Dependent Manner ◽  
Camp Formation ◽  
Pkc Activation ◽  
Stimulation Of

The present study examines the effects of 12-0-tetradecanoylphorbol-13-acetate (TPA) on agonist-regulated 3′, 5′-cyclic adenosine monophosphate (cAMP) formation and cAMP-mediated effects in cultured Sertoli cells from immature rats. Concentration-dependent stimulation of cAMP levels by follicle-stimulating hormone (FSH) was inhibited dramatically by the coaddition of 100 nmol/l TPA, which exerted a similar inhibition of glucagon- and isoproterenol-stimulated cAMP production. These results show that protein kinase C (PKC) activation by TPA attenuates Gs-protein-mediated agonist activation of cAMP production. (− )-N6(R)-Phenylisopropyladenosine (L-PIA), an A1-adenosine receptor agonist, inhibited cAMP stimulation by FSH in a concentration-dependent manner. When LPIA was added in increasing concentrations simultaneously with 100 nmol/l TPA, the L-PIA still inhibited FSH-stimulated cAMP production in a concentration-dependent manner. In the presence of TPA, the half-inhibitory concentration (IC50) for L-PIA inhibition of cAMP formation was reduced by more than one order of magnitude, indicating that PKC activation by TPA increases the sensitivity of Sertoli cells to G-protein-mediated agonist inhibition of cAMP production. The inhibitory effects of TPA on FSH-stimulated cAMP production were still observed when cAMP phosphodiesterase activity was inhibited by 1 mmol/l methylisobutylxanthine or when the activity of Gxi-protein was eliminated by pretreatment with 100 μg/l pertussis toxin. Taken together, the results indicate that PKC activation inhibits agonist-dependent stimulation of cAMP production by phosphorylation of components common to all the activating agonists used, and not via stimulation of Gi-protein activity or degradation of cAMP by cAMP phosphodiesterase activity. The increased sensitivity to L-PIA inhibition of cAMP formation induced by TPA may simply be a result of the reduced activity of the agonist-receptor/Gs-protein/C complex.

Potassium secretion by cortical collecting tubule: relation to sodium absorption, luminal sodium concentration, and transepithelial voltage

1981 ◽  
Vol 241 (4) ◽  
pp. F395-F402 ◽  
Author(s):  
J. B. Stokes
Keyword(s):  
Basolateral Membrane ◽  
Sodium Concentration ◽  
Sodium Absorption ◽  
Luminal Membrane ◽  
Rate Limiting Step ◽  
K Secretion ◽  
Potassium Secretion ◽  
Transepithelial Voltage ◽  
Collecting Tubules ◽  
Rate Limiting

Sodium absorption and K secretion were measured in isolated perfused rabbit cortical collecting tubules. To increase the range of transport rates some tubules were dissected from rabbit pretreated with DOcA. K secretin was unaffected by varying axial volume flow from 4 to 15 nl/min. K secretion was, however, correlated with transepithelial voltage and Na absorption. The Na:K transfer ratio was 1.35. In tubules dissected from normal rabbits, K secretion was almost eliminated by reducing Na concentration in the lumen to near 0 and was unaffected by varying luminal Na concentration from 30 to 145 mM. These data, together with other experimental results reported by several investigators, are consistent with a model for K secretion that places the rate-limiting step at the Na-K pump located on the basolateral membrane. The apical (luminal) membrane appears to be highly permeable to K.

Quinidine effect on hydrosmotic response of collecting tubules to vasopressin and cAMP

1987 ◽  
Vol 252 (6) ◽  
pp. F1103-F1111 ◽  
Author(s):  
M. Lorenzen ◽  
G. Frindt ◽  
A. Taylor ◽  
E. E. Windhager
Keyword(s):  
Water Permeability ◽  
Cytosolic Calcium ◽  
Toad Urinary Bladder ◽  
Similar Action ◽  
Cyclic Monophosphate ◽  
Ion Activity ◽  
Collecting Tubule ◽  
Quinidine Sulfate ◽  
Collecting Tubules ◽  
Dose Dependent

Quinidine, a compound thought to increase cytosolic calcium ion activity, has been found to inhibit the hydrosmotic response to vasopressin (VP) and adenosine 3',5'-cyclic monophosphate (cAMP) in the toad urinary bladder. To test whether this drug has a similar action in the mammalian nephron, the effect of quinidine on the hydraulic conductivity of the isolated perfused rabbit cortical collecting tubule (CCT) exposed to either 20 microU/ml VP or 10(-4) M 8-(p-chlorophenylthio) - adenosine 3',5' - cyclic monophosphate (8-CPT-cAMP) was studied. Quinidine had no effect on the basal water permeability of the CCT. Quinidine sulfate (10(-4) M) reduced the VP-stimulated water permeability from 280 +/- 50 X 10(-7) to 115 +/- 41 X 10(-7) cm X s-1 X atm-1 (P less than 0.05). The hydrosmotic response to 8-CPTcAMP was likewise reduced following exposure to quinidine. This effect was shown to be dose dependent. In paired experiments, inhibition of the response to 10(-4) M 8-CPTcAMP averaged 11% at 10(-6) M, 27% at 5 X 10(-6) M, 53% at 5 X 10(-5) M, and 50% at 10(-4) M quinidine. Inhibition of the response to 8-CPTcAMP was estimated to be half maximal at approximately 5 X 10(-6) M quinidine. Tubules were protected against the quinidine-induced inhibition by the addition of 6.5 X 10(-5) M quin 2-acetoxymethylester in the presence of low peritubular Ca concentration. These results are consistent with the view that elevated cytosolic Ca ion levels inhibit the increase in water permeability elicited by VP or exogenous cAMP in the mammalian CCT.

Temperature effect on ADH response of isolated perfused rabbit collecting tubules

1980 ◽  
Vol 239 (6) ◽  
pp. F595-F601 ◽  
Author(s):  
D. A. Hall ◽  
J. J. Grantham
Keyword(s):  
Water Absorption ◽  
Water Permeability ◽  
Time Course ◽  
Adenosine Monophosphate ◽  
Osmotic Gradient ◽  
Bathing Medium ◽  
Osmotic Water ◽  
Subsequent Response ◽  
Collecting Tubules ◽  
Peak Value

The time course of the water permeability response to synthetic arginine vasopressin (AVP) was examined in isolated perfused rabbit collecting tubules. When experiments were conducted at 37 degrees C, addition of AVP in a concentration of 100 microU/ml increased hydraulic water permeability (Lp) from 18 +/- 4 X 10(-7) to 153 +/- 15 X 10(-7) cm x s-1 x atm-1. However, in contrast to results obtained at 25 degrees C, the Lp immediately decreased in spite of the continued presence of AVP, reaching half the peak value in 67 +/- 6 (SE) min. A similar decline was observed at 37 degrees C when a cyclic 3',5'-adenosine monophosphate analogue was added to the bathing medium. Corticosteroids greatly enhanced the peak water absorption but did not stabilize the subsequent response to AVP at 37 degrees C. A decline in diffusional water permeability measured in the absence of a transtubule osmotic gradient excluded the possible roles of cellular hypotonicity, increased cell volume, or osmotic water absorption in the unstable response to hormone. The peritubular membrane remained highly permeable to water, independent of AVP and temperature. Duration of exposure to 37 degrees C was more important than AVP in determining the unstable response. On the basis of these studies we conclude that isolated rabbit cortical collecting tubules progressively become insensitive to AVP at 37 degrees C, possibly due to alterations in the responsiveness of the urinary plasma membrane to cAMP.

Parathyroid hormone is able to enhance cyclic adenosine monophosphate formation without causing an increase in cytoplasmic Ca2+ in osteoblasts

1993 ◽  
Vol 129 (2) ◽  
pp. 178-184 ◽  
Author(s):  
Östen Ljunggren ◽  
Hans Johansson ◽  
Peter Ridefelt ◽  
Ulf H Lerner ◽  
Erik Lindh ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cell Line ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Transient Increase ◽  
Osteosarcoma Cell Line ◽  
Osteosarcoma Cell ◽  
Human Osteoblasts ◽  
Camp Formation ◽  
Peak Value

There are several reports indicating that parathyroid hormone (PTH), besides inducing the formation of cyclic adenosine monophosphate (cAMP), also causes an increase in cytoplasmic free Ca2+ ([Ca2+]i) in osteoblasts, and it has been speculated that both of these second messengers are necessary to mediate PTH-induced bone resorption. In the osteoblastic cell line MC3T3-E1, bovine PTH 1–34 (10 nmol/l-1 μmol/l) stimulated cAMP formation but did not cause an increase in [Ca2+]i in adherent single cells (basal [Ca2+]i=151±5 nmol/l, mean±sem; N = 98). In contrast, subsequent addition of bradykinin (1 μmol/l) resulted in a transient increase in [Ca2+]i from a basal level of 155±11 nmol/l to a peak value of 351±60 nmol/l (N= 14). When the PTH challenge was followed by the addition of thrombin (10 U/ml), the latter induced a transient rise in [Ca2+]i from a basal level of 173±12 nmol/l to a peak at 341±33 nmol/l (N=20). Primary cultures of human osteoblasts were obtained from trabecular bone. These cells were also PTH-responsive in terms of cAMP formation. On the other hand, human PTH 1– 34 (100 nmol/l) did not affect [Ca2+]i in the isolated human osteoblasts, while bradykinin (1 μmol/l) caused a transient increase in [Ca2+]i (from a basal value of [Ca2+]i at 154±10 nmol/l to a peak value of 757±147 nmol/l within 30s;N= 16). Neither in the human osteosarcoma cell line SaOS-2 (basal value of [Ca2+]i at 94±10 nmol/l; N = 24), nor in the rat osteosarcoma cell line ROS 17/2.8 (basal value of [Ca2+]i at 85±9 nmol/l; N=9) was any effect of PTH (0.1 nmol/l-1 μmol/l) on [Ca2+]i demonstrated. In conclusion, we were unable to detect any effect of PTH on [Ca2+ ]i in single MC3T3-E1 cells, in isolated human osteoblasts, in SaOS-2 or in ROS 17/2.8 cells, whereas accumulation of cAMP was always seen. This indicates that cAMP is the major second messenger for PTH in osteoblasts.

Biphasic effect of interleukin-1β on arginine vasopressin-induced cellular cyclic adenosine monophosphate production in cultured rat renal papillary collecting tubule cells

1995 ◽  
Vol 132 (4) ◽  
pp. 472-478
Author(s):  
San-e Ishikawa ◽  
Toshikazu Saito
Keyword(s):  
Pertussis Toxin ◽  
Arginine Vasopressin ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Interleukin 1Β ◽  
Dependent Manner ◽  
Camp Production ◽  
Biphasic Effect ◽  
Collecting Tubule ◽  
Tubule Cells

Ishikawa S, Saito T. Biphasic effect of interleukin-1β on arginine vasopressin-induced cellular cyclic adenosine monophosphate production in cultured rat renal papillary collecting tubule cells. Eur J Endocrinol 1995;132:472–8. ISSN 0804–4643 The present study was undertaken to determine whether interleukin (IL)-1β affects the response of cellular cyclic adenosine monophosphate production to arginine vasopressin (AVP) in cultured rat renal papillary collecting tubule cells. Arginine vasopressin increased cellular cAMP production in a dose-dependent manner. A 10-min exposure of cells to IL-1β at a concentration of 1 × 10−12 mol/l or higher significantly reduced the AVP-induced increases in cellular cAMP production but did not affect the 2 × 10−8 mol/l forskolin-induced increases in cellular cAMP production. The IL-1β inhibition disappeared totally when cells were pretreated with 100 μg/1 pertussis toxin for 2 h. In contrast, more than a 30-min exposure of cells to IL-1β increased basal cAMP levels and enhanced both the AVP- and forskolin-induced increases in cellular cAMP production. These results indicate that IL-1β produces biphasic regulation of AVP-induced cellular cAMP production in renal papillary collecting tubule cells. The inhibition by IL-1β is dependent on the activation of pertussis toxin-sensitive G protein. However, the mechanism whereby the longer exposure to IL-1β enhances cAMP production remains to be determined. San-e Ishikawa, Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical School, 3311-1 Yakushiji Minamikawachi-machi, Tochigi 329-04. Japan

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