Voltage dependence and barium sensitivity of colonic K secretion in renal failure

1989 ◽  
Vol 256 (3) ◽  
pp. F490-F496 ◽  
Author(s):  
E. L. Siga ◽  
R. S. Martin ◽  
C. Ibarra ◽  
D. Veron ◽  
F. Ibarra ◽  
...  
Keyword(s):  
Renal Failure ◽  
Active Transport ◽  
Voltage Dependence ◽  
Apical Membrane ◽  
Distal Colon ◽  
K Channels ◽  
K Secretion ◽  
Stimulation Of

Net colonic K secretion (JKnet) is increased in rats and humans with chronic renal failure (CRF). To study whether transepithelial potential difference (PD), active transport forces and/or luminal K conductance play a role in this adaptation, experiments were performed in the colon of control, K-adapted, and CRF rats. Under basal conditions the PD in vivo in CRF was greater than in controls and not different from K-adapted rats. JKnet was comparable in vivo in CRF and K-adapted rats and was greater than in controls. Amiloride (10 microM) reduced PD and JKnet in K-adapted and CRF rats to levels comparable to controls. Under in vitro short-circuited conditions serosal-to-mucosal K flux (JKs----m) in distal colon was significantly increased in K-adapted and CRF animals compared with control, whereas barium caused a significant reduction in JKs----m in all groups of animals. The barium-sensitive component of K secretion was greater, however, in the two experimental groups (-0.2 +/- 0.02 and -0.2 +/- 0.07 in K-adapted and CRF animals, respectively, vs. -0.08 +/- 0.02 microeq.h-1.cm-2 in controls, P less than 0.05). However, luminal barium failed to completely inhibit the increase in K secretion observed in the experimental groups. These data suggest that an increase in PD that results in a rise in luminal negativity, stimulation of active transport, and an increase in barium-sensitive K channels and barium-insensitive pathways in apical membrane of distal colon participate in the mechanism by which net K secretion is increased in the large intestine of subjects with CRF.

Low-dose glucocorticoids maintain Na-H exchange in distal colon of adrenalectomized rats

1991 ◽  
Vol 261 (3) ◽  
pp. F545-F553 ◽  
Author(s):  
C. P. Bastl ◽  
L. Bressler ◽  
G. Schulman ◽  
M. Mendez ◽  
E. J. Cragoe
Keyword(s):  
Short Circuit ◽  
In Vitro Study ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Ion Flux ◽  
Rat Colon ◽  
Anion Secretion ◽  
Stimulation Of

With in vivo perfusion we demonstrated that physiological doses of glucocorticoids restore Na and Cl absorption in adrenalectomized rat colon. The absorption is spironolactone and amiloride resistant and is inhibited by the Na-H inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), suggesting that glucocorticoids modulate Na-H antiport. The present in vitro study examines pathways mediated by glucocorticoids in adrenalectomized rat distal colon and rectum. In vivo administration of 2.5 micrograms/100 g body wt dexamethasone did not alter serosal-to-mucosal flux or tissue electrical parameters but restored mucosal-to-serosal flux and net Na and Cl absorption within 2–3 h of administration to levels found in intact rat colon. Transport was not inhibited by 10(-5) M amiloride but was eliminated by 10(-5) M EIPA. After 26 h of dexamethasone, an amiloride-resistant short-circuit current was stimulated, accompanied by increased residual ion flux in rectum, but not distal colon, suggesting that a delayed or secondary effect of glucocorticoids is stimulation of electrogenic anion secretion. Thus adrenalectomy reduces net ion flux in distal colon by its effect on electroneutral mucosal-to-serosal NaCl flux. Small doses of glucocorticoids completely ameliorate this effect via stimulation of the Na-H antiport. Glucocorticoids maintain basal electroneutral NaCl absorption in distal rat colon.

scholarly journals The characteristics of intracellular Ca2+ signals in vivo necessitate a new model for salivary fluid secretion

2021 ◽  
Author(s):  
Takahiro Takano ◽  
Amanda M. Wahl ◽  
Kai-Ting Huang ◽  
John Rugis ◽  
James Sneyd ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Fluid Secretion ◽  
Salivary Secretion ◽  
Apical Region ◽  
Isolated Cells ◽  
Marked Contrast ◽  
K Channels ◽  
Stimulation Of

AbstractSalivary fluid secretion involves an intricate choreography to result in the trans-epithelial movement of NaCl and water into the acinus lumen. Current models are based on experimental observations in enzymatically isolated cells where the Ca2+ signal invariably propagates globally and thus appears ideally suited to activate spatially separated Cl and K channels. We monitored Ca2+ signals and salivary secretion in live mice expressing GCamp6F, following stimulation of the nerves innervating the submandibular gland. Consistent with in vitro studies, Ca2+ signals were initiated in the apical endoplasmic reticulum. In marked contrast to in vitro data, highly localized trains of Ca2+ transients that failed to propagate from the apical region were observed. Following stimuli optimum for secretion, large apical-basal gradients were elicited. Given this incompatibility to the previous model, a new mathematical model was constructed to explain how salivary secretion can be efficiently stimulated by apically localized Ca2+ signals.

Evidence for an Increased Generation of Prostacyclin in the Microvasculature and an Impairment of the Platelet α-Granule Release in Chronic Renal Failure

1988 ◽  
Vol 60 (02) ◽  
pp. 205-208 ◽  
Author(s):  
Paul A Kyrle ◽  
Felix Stockenhuber ◽  
Brigitte Brenner ◽  
Heinz Gössinger ◽  
Christian Korninger ◽  
...  
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Blood Clotting ◽  
Normal Subjects ◽  
Chronic Uraemia ◽  
Wall Interaction ◽  
End Stage ◽  
Granule Release

SummaryThe formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the micro vasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1α (6-keto-PGF1α) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the a-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is - at least partially - due to an acquired defect of the platelet a-granule release and an increased generation of PGI2 in the micro vasculature.

Thrombopoietin-Induced Stimulation of Megakaryocyte- Enriched Bone Marrow Cultures

1979 ◽  
Author(s):  
K. L. Kellar ◽  
B. L. Evatt ◽  
C. R. McGrath ◽  
R. B. Ramsey
Keyword(s):  
Bone Marrow ◽  
Dna Synthesis ◽  
Bone Marrow Cells ◽  
Rabbit Plasma ◽  
Bone Marrow Cultures ◽  
Plasma Fractions ◽  
Marrow Cultures ◽  
Stimulation Of

Liquid cultures of bone marrow cells enriched for megakaryocytes were assayed for incorporation of 3H-thymidine (3H-TdR) into acid-precipitable cell digests to determine the effect of thrombopoietin on DNA synthesis. As previously described, thrombopoietin was prepared by ammonium sulfate fractionation of pooled plasma obtained from thrombocytopenic rabbits. A control fraction was prepared from normal rabbit plasma. The thrombopoietic activity of these fractions was determined in vivo with normal rabbits as assay animals and the rate of incorporation of 75Se-selenomethionine into newly formed platelets as an index of thrombopoietic activity of the infused material. Guinea pig megakaryocytes were purified using bovine serum albumin gradients. Bone marrow cultures containing 1.5-3.0x104 cells and 31%-71% megakaryocytes were incubated 18 h in modified Dulbecco’s MEM containing 10% of the concentrated plasma fractions from either thrombocytopenic or normal rabbits. In other control cultures, 0.9% NaCl was substituted for the plasma fractions. 3H-TdR incorporation was measured after cells were incubated for 3 h with 1 μCi/ml. The protein fraction containing thrombopoietin-stimulating activity caused a 25%-31% increase in 3H-TdR incorporation over that in cultures which were incubated with the similar fraction from normal plasma and a 29% increase over the activity in control cultures to which 0.9% NaCl had been added. These data suggest that thrombopoietin stimulates DNA synthesis in megakaryocytes and that this tecnique may be useful in assaying thrombopoietin in vitro.

scholarly journals Contamination of erythropoietin by endotoxin: in vivo and in vitro effects on murine erythropoiesis

Blood ◽  
1979 ◽  
Vol 54 (1) ◽  
pp. 146-158 ◽  
Author(s):  
KS Zuckerman ◽  
PJ Quesenberry ◽  
J Levin ◽  
R Sullivan
Keyword(s):  
Significant Inhibition ◽  
Erythropoietic Activity ◽  
Limulus Amebocyte Lysate ◽  
Endogenous Erythropoietin ◽  
Significant Change ◽  
In Vitro Effects ◽  
Stimulation Of

Abstract Endotoxin was detected in all erythropoietin preparations tested and was removed from four lots, without loss of erythropoietic activity, by adsorption with limulus amebocyte lysate. Comparison of adsorbed (endotoxin-depleted) and nonadsorbed (endotoxin-containing) erythropoietin preparations demonstrated significant inhibition of CFU- e and BFU-e in vitro by nonadsorbed erythropoietin at concentrations higher than 0.25 U/ml and 2.0 U/ml, respectively. CFU-e and BFU-e were inhibited significantly by readdition in vitro of 10(-5)-10(-3) mug of endotoxin per unit of limulus-adsorbed erythropoietin. Administration of saline or 6 U of nonadsorbed or adsorbed erythropoietin twice a day for 4 days of CF1 mice resulted in reticulocyte counts of 2.1%, 9.9%, and 15.9%, respectively. Nonadsorbed erythropoietin resulted in a 29% decrease in erythropoiesis, a 42% decrease in CFU-e, and a 16% increase in granulopoiesis in the marrow, whereas adsorbed erythropoietin caused a 28% increase in erythropoiesis, no significant change in CFU-e and a 19% decrease in granulopoiesis in the marrow. Both preparations resulted in marked increases in splenic erythropoiesis and granulopoiesis. The effects of adsorbed erythropoietin are similar to those produced following stimulation of hematopoiesis by endogenous erythropoietin. Hemopoietic changes induced by nonadsorbed erythropoietin in vivo and in vitro are affected substantially by contamination of the erythropoietin preparations with endotoxin.

Metabolic importance of Na+/K+-ATPase activity during sea urchin development.

1997 ◽  
Vol 200 (22) ◽  
pp. 2881-2892 ◽  
Author(s):  
P Leong ◽  
D Manahan
Keyword(s):  
Enzyme Activity ◽  
Atpase Activity ◽  
Sea Urchin ◽  
Sodium Pump ◽  
Sea Water ◽  
Strongylocentrotus Purpuratus ◽  
Lytechinus Pictus ◽  
Stimulation Of

Early stages of animal development have high mass-specific rates of metabolism. The biochemical processes that establish metabolic rate and how these processes change during development are not understood. In this study, changes in Na+/K+-ATPase activity (the sodium pump) and rate of oxygen consumption were measured during embryonic and early larval development for two species of sea urchin, Strongylocentrotus purpuratus and Lytechinus pictus. Total (in vitro) Na+/K+-ATPase activity increased during development and could potentially account for up to 77 % of larval oxygen consumption in Strongylocentrotus purpuratus (pluteus stage) and 80 % in Lytechinus pictus (prism stage). The critical issue was addressed of what percentage of total enzyme activity is physiologically active in living embryos and larvae and thus what percentage of metabolism is established by the activity of the sodium pump during development. Early developmental stages of sea urchins are ideal for understanding the in vivo metabolic importance of Na+/K+-ATPase because of their small size and high permeability to radioactive tracers (86Rb+) added to sea water. A comparison of total and in vivo Na+/K+-ATPase activities revealed that approximately half of the total activity was utilized in vivo. The remainder represented a functionally active reserve that was subject to regulation, as verified by stimulation of in vivo Na+/K+-ATPase activity in the presence of the ionophore monensin. In the presence of monensin, in vivo Na+/K+-ATPase activities in embryos of S. purpuratus increased to 94 % of the maximum enzyme activity measured in vitro. Stimulation of in vivo Na+/K+-ATPase activity was also observed in the presence of dissolved alanine, presumably due to the requirement to remove the additional intracellular Na+ that was cotransported with alanine from sea water. The metabolic cost of maintaining the ionic balance was found to be high, with this process alone accounting for 40 % of the metabolic rate of sea urchin larvae (based on the measured fraction of total Na+/K+-ATPase that is physiologically active in larvae of S. purpuratus). Ontogenetic changes in pump activity and environmentally induced regulation of reserve Na+/K+-ATPase activity are important factors that determine a major proportion of the metabolic costs of sea urchin development.

scholarly journals A Selective TSH Receptor Antagonist Inhibits Stimulation of Thyroid Function in Female Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 310-314 ◽  
Author(s):  
Susanne Neumann ◽  
Eshel A. Nir ◽  
Elena Eliseeva ◽  
Wenwei Huang ◽  
Juan Marugan ◽  
...  
Keyword(s):  
Small Molecule ◽  
Sodium Iodide ◽  
Cell System ◽  
Tsh Receptor ◽  
Free T4 ◽  
Serum Free ◽  
Stimulation Of ◽  
Lowered Serum

Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease.

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