Effect of protamine on ion conductance of upper portion of descending limb of long-looped nephron from hamsters

1991 ◽  
Vol 260 (6) ◽  
pp. F839-F847 ◽  
Author(s):  
S. Koyama ◽  
K. Yoshitomi ◽  
M. Imai
Keyword(s):  
Control Level ◽  
Transference Number ◽  
Inhibitory Effect ◽  
Shunt Resistance ◽  
Ion Conductance ◽  
Selective Permeability ◽  
Nacl Concentration ◽  
Diffusion Voltage ◽  
Salt Diffusion ◽  
Paracellular Shunt

To estimate the contribution of paracellular shunt pathway to the cation-selective permeability in the upper portion of the descending limb of long-looped nephron (LDLu) of hamsters, we observed the effect of protamine on salt-diffusion voltage (delta VT) and transmural resistance (RT). delta VT generated on reduction of lumen NaCl concentration was decreased from 12.0 +/- 1.4 to 7.3 +/- 1.2 mV when 100 micrograms/ml protamine were added to the lumen. Although the effect of protamine persisted after removal of the agent from the lumen, addition of 30 U/ml heparin reversed the delta VT toward the control level. The effect of protamine was dose dependent in the range from 3 to 1,000 micrograms/ml. Protamine was without effect from the bath. Studies on single salt dilution voltage revealed that 100 and 300 micrograms/ml protamine inhibited relative Na+ to Cl- permeability from 4.03 +/- 0.38 to 2.14 +/- 0.21 and from 3.75 +/- 0.37 to 1.36 +/- 0.09, respectively. Protamine markedly decreased the apparent transference number for Na+ but slightly increased the value for Cl-. Protamine also inhibited permeabilities for K+, Rb+, and Li+ relative to Cl-, indicating that the inhibitory effect of protamine was not confined to Na+ but was generalized to cations. Transmural cable analysis showed that 100 micrograms/ml protamine increased RT from 14.0 +/- 1.1 to 19.3 +/- 1.2 omega.cm2, with the effect being reversed by 30 U/ml heparin. Because the effect of protamine on RT was unaffected by ouabain in the bath, changes in RT may mainly represent those of the paracellular shunt resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of protamine on ion conductance of ascending thin limb of Henle's loop from hamsters

1991 ◽  
Vol 261 (4) ◽  
pp. F593-F599 ◽  
Author(s):  
S. Koyama ◽  
K. Yoshitomi ◽  
M. Imai
Keyword(s):  
Control Level ◽  
Transference Number ◽  
Inhibitory Effect ◽  
Ion Conductance ◽  
Nacl Concentration ◽  
Diffusion Voltage ◽  
Salt Diffusion ◽  
Dose Dependent ◽  
Thin Limb

To evaluate the contribution of paracellular shunt pathway in ascending thin limb (ATL) of hamsters, we examined the effect of protamine, a selective blocker of paracellular conductance, on salt-diffusion voltage (dVT) and transmural resistance (RT) during in vitro microperfusion. Lumen-negative dVT generated on reduction of lumen NaCl concentration was increased further from -7.3 +/- 0.5 to -10.3 +/- 0.7 mV when 300 micrograms/ml protamine was added to the lumen, and calculated Na+/Cl- permeability ratio was decreased from 0.46 +/- 0.03 to 0.31 +/- 0.03. Although the effect of protamine persisted after removal of the agent from the lumen, addition of 30 U/ml heparin returned the dVT toward the control level. The effect of protamine was dose dependent from 30 to 300 micrograms/ml. Protamine also exerted its effect from the bath, and the effect was inhibited by heparin either from the lumen or from the bath. The inhibitory effect was almost the same when the orientation of imposed NaCl gradient was reversed. Inhibition of transcellular Cl- transport with 0.1 mM 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) in the bath caused lumen-positive dVT. This voltage was decreased significantly by protamine. Protamine markedly decreased the apparent transference number for Na+ but slightly increased the value for Cl-. Transmural cable analysis showed that 300 micrograms/ml protamine added to the lumen increased RT from 0.59 +/- 0.10 to 1.20 +/- 0.20 omega.cm2, with the effect being reversed by 30 U/ml heparin.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effect of dimethyl sulfoxide on human carcinoma cells, inhibition of plasminogen activator synthesis, change in cell morphology, and alteration of response to cholera toxin.

1985 ◽  
Vol 5 (12) ◽  
pp. 3552-3559 ◽  
Author(s):  
L Ossowski ◽  
D Belin
Keyword(s):  
Dimethyl Sulfoxide ◽  
Cholera Toxin ◽  
Plasminogen Activator ◽  
Cell Morphology ◽  
Control Level ◽  
Metastatic Potential ◽  
Inhibitory Effect ◽  
Human Carcinoma ◽  
Enhanced Production

Human carcinoma HEp-3 lost its tumorigenic and metastatic potential upon prolonged culture in vitro. This change was accompanied by a reduced production of plasminogen activator (PA) of the urokinase type (uPA), which is secreted by HEp-3 cells, a change in response to effectors that modulate uPA production, and an alteration of cell morphology. Similar but more rapid changes occurred when malignant HEp-3 cells were exposed to dimethyl sulfoxide (DMSO). uPA activity in the culture medium dropped below 50% of the control level within 6 h after the addition of DMSO and became undetectable after 24 h of treatment. This drop in uPA activity was not caused by an increased production of PA inhibitors. The cell-associated uPA decreased to 25 to 30% of the control level within 6 h of DMSO treatment and remained at this level for at least 96 h; the reduced uPA production was partially accounted for by a rapid decrease in the functional and chemical concentration of uPA mRNA. In contrast, the concentrations of most of the abundant mRNA species did not appear to be significantly affected, and cell growth was only slightly inhibited in the presence of DMSO. Malignant HEp-3 cells treated with DMSO responded to cholera toxin with an enhanced production of uPA, and their morphology became indistinguishable from that of nonmalignant HEp-3 cells grown in vitro for prolonged periods of time. All of the above changes were fully and rapidly reversible. The inhibitory effect of DMSO on PA production appears to be specific for uPA of human cell lines.

Ca2+-dependent desensitization of insulin secretion by strong potassium depolarization

2012 ◽  
Vol 303 (2) ◽  
pp. E223-E233 ◽  
Author(s):  
M. Willenborg ◽  
M. Belz ◽  
K. Schumacher ◽  
A. Paufler ◽  
K. Hatlapatka ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Concentration ◽  
Choline Chloride ◽  
Inhibitory Effect ◽  
High K ◽  
Nacl Concentration ◽  
Voltage Dependent ◽  
Fast Decline ◽  
Insulinotropic Effect ◽  
Initial Peak

Depolarization by a high K+ concentration is a widely used experimental tool to stimulate insulin secretion. The effects occurring after the initial rise in secretion were investigated here. After the initial peak a fast decline occurred, which was followed by a slowly progressive decrease in secretion when a strong K+ depolarization was used. At 40 mM KCl, but not at lower concentrations, the decrease continued when the glucose concentration was raised from 5 to 10 mM, suggesting an inhibitory effect of the K+ depolarization. When tolbutamide was added instead of the glucose concentration being raised, a complete inhibition down to prestimulatory values was observed. Equimolar reduction of the NaCl concentration to preserve isoosmolarity enabled an increase in secretion in response to glucose. Unexpectedly, the same was true when the Na+-reduced media were made hyperosmolar by choline chloride or mannitol. The insulinotropic effect of tolbutamide was not rescued by the compensatory reduction of NaCl, suggesting a requirement for activated energy metabolism. These inhibitory effects could not be explained by a lack of depolarizing strength or by a diminished free cytosolic Ca2+ concentration ([Ca2+]i). Rather, the complexation of extracellular Ca2+ concomitant with the K+ depolarization markedly diminished [Ca2+]i and attenuated the inhibitory action of 40 mM KCl. This suggests that a strong but not a moderate depolarization by K+ induces a [Ca2+]i-dependent, slowly progressive desensitization of the secretory machinery. In contrast, the decline immediately following the initial peak of secretion may result from the inactivation of voltage-dependent Ca2+ channels.

scholarly journals Mechanisms of zinc uptake in gills of freshwater rainbow trout: interplay with calcium transport

1996 ◽  
Vol 270 (5) ◽  
pp. R1141-R1147 ◽  
Author(s):  
C. Hogstrand ◽  
P. M. Verbost ◽  
S. E. Bonga ◽  
C. M. Wood
Keyword(s):  
Rainbow Trout ◽  
Control Level ◽  
Inhibitory Effect ◽  
Chloride Cells ◽  
Water Addition ◽  
Uptake Mechanism ◽  
Basolateral Membranes ◽  
Control Value

The uptake mechanism of Zn2+ through the gill epithelium of freshwater rainbow trout was investigated both in intact animals and in isolated basolateral membranes. Involvement of the apical Ca2+ uptake sites in Zn2+ uptake was examined in vivo by pharmacological manipulation of the apical Ca2+ permeability. The apical entries of Ca2+ and Zn2+, but not Na2+ and Cl-, were inhibited by addition of La to the water. Addition of 1.0 microM La reduced the influxes of Ca2+ and Zn2+ to 22 +/- 3 and 53 +/- 7% (mean +/- SE) of the control value, respectively. Injection of CaCl2 also reduced the branchial influxes of Ca2+ and Zn2+. This treatment decreased the influx of Ca2- to 45 +/- 4% of the control level and the Zn2+ influx to 68 +/- 5%. These results strongly imply that Zn2+ passes across the apical membrane of the chloride cells of the gills via the same pathway as Ca2+. The presence of an active basolateral transporter for Zn2+ was investigated in vitro on isolated basolateral membranes. There was no ATP-dependent or Na2+(-)gradient driven transport of Zn2+ at physiological Zn2+ activities. The same system was used to study potential effects of Zn2+ on the basolateral Ca2+(-)adenosinetri-phosphatase. Zn2+ was found to be a potent blocker of this transporter, causing a mixed inhibitory effect on the ATP driven Ca2+ transport at a free Zn2+ activity of 100 pM.

scholarly journals Effects of potassium deficiency on growth and protein synthesis in skeletal muscle and the heart of rats

1989 ◽  
Vol 62 (2) ◽  
pp. 269-284 ◽  
Author(s):  
Inge Dôrup ◽  
Torben Clausen
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Control Level ◽  
Inhibitory Effect ◽  
Potassium Deficiency ◽  
Skeletal Muscle Protein ◽  
K Deficiency

The effects of potassium deficiency on growth, K content and protein synthesis have been compared in 4–13-week-old rats. When maintained on K-deficient fodder (1 mmol/kg) rats ceased to grow within a few days, and the incorporation of [3H]leucine into skeletal muscle protein in vivo was reduced by 28–38%. Pair-feeding experiments showed that this inhibition was not due to reduced energy intake. Following 14 d on K-deficient fodder, there was a further reduction (39–56 %) in the incorporation of [3H]leucine into skeletal muscle protein, whereas the incorporation into plasma, heart and liver proteins was not affected. The accumulation of the non-metabolized amino acid α-aminoisobutyric acid in the heart and skeletal muscles was not reduced. The inhibitory effect of K deficiency on 3H-labelling of muscle protein was seen following intraperitoneal (10–240 min) as well as intravenous (10 min) injection of [3H]leucine. In addition, the incorporation of [3H]phenylalanine into skeletal muscle protein was reduced in K-depleted animals. Following acute K repletion in vivo leading to complete normalization of muscle K content, the incorporation of [3H]leucine into muscle protein showed no increase within 2 h, but reached 76 and 104% of the control level within 24 and 72 h respectively. This was associated with a rapid initial weight gain, but normal body-weight was not reached until after 7 weeks of K repletion. Following 7 d on K-deficient fodder the inhibition of growth and protein synthesis was closely correlated with the K content of the fodder (1–40 mmol/kg) and significant already at modest reductions in muscle K content. In vitro experiments with soleus muscle showed a linear relationship between the incorporation of [3H]leucine into muscle protein and K content, but the sensitivity to cellular K deficiency induced in vitro was much less pronounced than that induced in vivo. Thus, in soleus and extensor digitorum longus (EDL) muscles prepared from K-deficient rats, the incorporation of [3H]leucine was reduced by 30 and 47 % respectively. This defect was completely restored by 24 h K repletion in vivo. It is concluded that in the intact organism protein synthesis and growth are very sensitive to dietary K deficiency and that this can only partly be accounted for by the reduction in cellular K content per se. The observations emphasize the need for adequate K supplies to ensure optimum utilization of food elements for protein synthesis and growth.

scholarly journals Effect of Nitric Oxide Blockade by NG-Nitro-l-Arginine on Cerebral Blood Flow Response to Changes in Carbon Dioxide Tension

1992 ◽  
Vol 12 (6) ◽  
pp. 947-953 ◽  
Author(s):  
Qiong Wang ◽  
Olaf B. Paulson ◽  
Niels A. Lassen
Keyword(s):  
Nitric Oxide ◽  
Carbon Dioxide ◽  
Blood Pressure ◽  
Control Level ◽  
Inhibitory Effect ◽  
Carbon Dioxide Tension ◽  
Extracellular Acidosis ◽  
Flow Response ◽  
Arterial Blood ◽  
Oxide Synthase

The importance of nitric oxide (NO) for CBF variations associated with arterial carbon dioxide changes was investigated in halothane-anesthetized rats by using an inhibitor of nitric oxide synthase, NG-nitro-l-arginine (NOLAG). CBF was measured by intracarotid injection of 133Xe. In normocapnia, intracarotid infusion of 1.5, or 7.5, or 30 mg/kg NOLAG induced a dose-dependent increase of arterial blood pressure and a decrease of normocapnic CBF from 85 ± 10 to 78 ± 6, 64 ± 5, and 52 ± 5 ml 100g−1 min−1, respectively. This effect lasted for at least 2 h. Raising Paco2 from a control level of 40 to 68 mm Hg increased CBF to 230 ± 27 ml 100g−1 min−1, corresponding to a percentage CBF response (CO2 reactivity) of 3.7 ± 0.6%/mm Hg Paco2 in saline-treated rats. NOLAG attenuated this reactivity by 32, 49, and 51% at the three-dose levels. Hypercapnia combined with angiotensin to raise blood pressure to the same level as the highest dose of NOLAG did not affect the CBF response to hypercapnia. l-Arginine significantly prevented the effect of NOLAG on normocapnic CBF as well as blood pressure and also abolished its inhibitory effect on hypercapnic CBF. d-Arginine had no such effect. Decreasing Paco2 to 20 mm Hg reduced control CBF to 46 ± 3 ml 100g−1 min−1 with no further reduction after NOLAG. Furthermore, NOLAG did not change the percentage CBF response to an extracellular acidosis induced by acetazolamide (50 mg/kg). The results suggest that NO or a closely related compound is involved in the regulation of CBF in normocapnia and even more so in hypercapnia.

Paradoxical effect of perchlorate on thyroidal weight, glucose 6-phosphate dehydrogenase and polyamines in methylthiouracil-treated rats

1981 ◽  
Vol 97 (4) ◽  
pp. 491-495 ◽  
Author(s):  
S. Matsuzaki ◽  
M. Suzuki
Keyword(s):  
Enzyme Activity ◽  
Control Level ◽  
Sodium Perchlorate ◽  
Inhibitory Effect ◽  
Paradoxical Effect ◽  
G6pdh Activity ◽  
Wet Weight ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract. The effect of sodium perchlorate (NaClO4) on the methylthiouracil-induced increase in the activity of thyroid glucose 6-phosphate dehydrogenase (G6PDH), ornithine decarboxylase (ODC) and polyamine contents was studied in the rat. The G6PDH activity was increased nearly three-fold by methylthiouracil (MTU) but not by ClO4- at 7 days of treatment. Perchlorate lowered the MTU-induced enzyme activity to nearly the control level, without changing circulating thyrotrophin (TSH). The anion had no inhibitory effect on G6PDH activity in vitro. The possibility that an inhibitor specific for G6PDH was generated in ClO4- treated rat thyroids was excluded. The activity of ODC was greatly increased by both ClO4- and MTU, the increase being significant as early as on the second day of treatment. Perchlorate had no inhibitory effect on MTU-induced ODC activity in vivo but decreased total contents of spermidine and spermine in the thyroid, without affecting the concentration (nmoles/ g wet weight) of the polyamines. These results suggest that ClO4- acts directly on the thyroid to suppress specifically the stimulatory effect of TSH on G6PDH activity and possibly on polyamine accumulation.

Interaction of heptanol and pressure on sodium and chloride transport by toad skin

1990 ◽  
Vol 69 (5) ◽  
pp. 1883-1892 ◽  
Author(s):  
M. Li ◽  
S. K. Hong ◽  
J. M. Goldinger ◽  
M. E. Duffey
Keyword(s):  
Channel Blocker ◽  
Chloride Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Na Transport ◽  
Toad Skin ◽  
Shunt Resistance ◽  
Cl Conductance

We examined the interaction of heptanol and hydrostatic pressure on Na+ and Cl- transport in isolated toad skin. In the presence of Cl-, heptanol decreased short-circuit current (Isc) and total transepithelial resistance (Rt). However, in the absence of Cl- in the mucosal bath, heptanol increased Rt, although it retained the same inhibitory effect on Isc. When transepithelial active Na+ transport was blocked by amiloride, heptanol had no effect on Isc whether or not Cl- was present, whereas it decreased the shunt resistance (Rs) only in the presence of Cl- in the mucosal bath. Moreover, this effect of heptanol on Rs was significantly smaller in the presence of diphenylamine-2-carboxylate (DPC), a known Cl- channel blocker. Pressure also decreased Isc through inhibition of active Na+ transport, but it increased Rs. When heptanol and pressure were applied together, their inhibitory effects on Isc were additive, but their effects on Rs were antagonistic. Furthermore, when a transepithelial Cl- current was produced by reducing the Cl- concentration of the serosal bath, heptanol stimulated this current, which was reversibly inhibited by pressure or DPC addition to the mucosal bath. When the heptanol-stimulated Cl- current was first inhibited by pressure, subsequent DPC addition had less or no effect. These results suggest that one site of an antagonistic interaction of heptanol and pressure in toad skin is an apical membrane Cl- conductance.

Inhibition of vascular smooth muscle cell proliferation by chronic hemin treatment

2008 ◽  
Vol 295 (3) ◽  
pp. H999-H1007 ◽  
Author(s):  
Tuanjie Chang ◽  
Lingyun Wu ◽  
Rui Wang
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Cell Cycle Progression ◽  
Control Level ◽  
Inhibitory Effect ◽  
Cycle Progression ◽  
Vsmc Proliferation ◽  
Long Term Treatment

Hemin, an oxidized form of heme, is an essential regulator of gene expression and cell cycle progression. Our laboratory previously reported ( 34 ) that chronic hemin treatment of spontaneously hypertensive rats reversed the eutrophic inward remodeling of small peripheral arteries. Whether long-term treatment of cultured vascular smooth muscle cells (VSMCs) with hemin alters the proliferation status of these cells has been unknown. In the present study, hemin treatment at 5 μM for 4, 7, 14, and 21 days significantly inhibited the proliferation of cultured rat aortic VSMCs (A-10 cells) by arresting cells at G0/G1 phases so as to decelerate cell cycle progression. Heme oxygenase (HO) activity and inducible HO-1 protein expression were significantly increased by hemin treatment. HO inhibitor tin protoporphyrin IX (SnPP) abolished the effects of hemin on cell proliferation and HO activity. Interestingly, hemin-induced HO-1 expression was further increased in the presence of SnPP. Hemin treatment had no significant effect on the expression of constitutive HO-2. Expression of p21 protein and the level of reactive oxygen species (ROS) were decreased by hemin treatment, which was reversed by application of SnPP. After removal of hemin from culture medium, inhibited cell proliferation and increased HO-1 expression in VSMCs were returned to control level within 1 wk. Transfection with HO-1 small interfering RNA significantly knocked down HO-1 expression and decreased HO activity, but had no effect on HO-2 expression, in cells treated with or without hemin for 7 days. The inhibitory effect of hemin on cell proliferation was abolished in HO-1 silenced cells. It is concluded that induction of HO-1 and, consequently, increased HO activity are responsible for the chronic inhibitory effect of hemin on VSMC proliferation. Changes in the levels of p21 and ROS might also participate in the cellular effects of hemin.

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