Physiological effect of protein kinase C on ENaC-mediated lung liquid regulation in the adult rat lung

2012 ◽  
Vol 302 (1) ◽  
pp. L133-L139 ◽  
Author(s):  
Benjamin Soukup ◽  
Audra Benjamin ◽  
Maria Orogo-Wenn ◽  
Dafydd Walters
Keyword(s):  
Control Period ◽  
Inhibitory Effect ◽  
Ringer Solution ◽  
Physiological Effect ◽  
Physiological Regulation ◽  
Pkc Inhibitor ◽  
Downstream Target ◽  
Adult Rat ◽  
Lung Liquid ◽  
Pkc Activation

Tight control of lung liquid (LL) regulation is vital for pulmonary function. The aim of this work was to determine whether PKC activation is involved in the physiological regulation of LL volume in a whole lung preparation. Rat lungs were perfused with a modified Ringer solution, and the lumen was filled with the same solution without glucose. LL volume was measured during a control period and after modulating drugs were administered, and net LL transepithelial movement ( Jv) was calculated. When the PKC activator PMA (10−5 M) and the Ca2+ ionophore ionomycin (10−6 M) were instilled into the lung together, Jv was significantly reduced ( P = 0.03). This reduction was blocked by the PKC inhibitor chelerythrine chloride (10−6 M; P = 0.56) and by a second PKC inhibitor GF109203X (10−5 M; P = 0.98). When PMA and ionomycin were added with the β-adrenergic agonist terbutaline, the terbutaline-induced increase in Jv was abolished. Addition of PMA and ionomycin with the epithelial Na+ channel (ENaC) blocker amiloride had no additional inhibitory effect. Together, these results suggest that PKC is likely to be involved in LL absorption, and the ability of PMA/ionomycin to block the terbutaline-induced increase in Jv suggests that the downstream target of PKC is ENaC.

Amiloride blocks the inhibition of fetal lung liquid secretion caused by AVP but not by asphyxia

1993 ◽  
Vol 74 (1) ◽  
pp. 111-115 ◽  
Author(s):  
S. B. Hooper ◽  
M. J. Wallace ◽  
R. Harding
Keyword(s):  
Control Period ◽  
Fetal Lung ◽  
Inhibitory Effect ◽  
Luminal Surface ◽  
Na Channels ◽  
Inhibitory Effects ◽  
Fetal Sheep ◽  
Pulmonary Epithelial Cells ◽  
Lung Liquid ◽  
Secretion Rates

We have examined whether the activation of Na+ channels, located on the luminal surface of pulmonary epithelial cells, mediates the inhibitory effects of both arginine vasopressin (AVP) and moderate asphyxia on fetal lung liquid secretion. Lung liquid secretion rates were measured in chronically catheterized fetal sheep during AVP infusions and during periods of asphyxia with and without an Na+ transport blocker (amiloride; 10(-4) M) present in lung liquid. Lung liquid secretion rates were also measured during epinephrine infusions with amiloride present in lung liquid. These secretion rates were compared with measurements made during a preceding control period. Both asphyxia and an infusion of AVP significantly reduced the rate of secretion of fetal lung liquid from 8.4 +/- 1.5 and 18.0 +/- 3.7 to 3.6 +/- 1.0 (P < 0.01) and 5.5 +/- 2.1 ml/h (P < 0.01), respectively. The addition of amiloride to lung liquid did not reverse the inhibitory effects of asphyxia on lung liquid secretion (8.6 +/- 0.8 vs. 0.7 +/- 0.4 ml/h) but did block the inhibitory effects of both epinephrine (14.8 +/- 4.4 vs. 13.8 +/- 3.1 ml/h) and AVP (18.0 +/- 3.7 vs. 19.5 +/- 5.0 ml/h). The addition of amiloride to lung liquid during fetal normoxia did not significantly affect fetal lung liquid secretion rates (8.2 +/- 1.1 vs. 7.4 +/- 0.7 ml/h). We conclude that the inhibitory effect of AVP on fetal lung liquid secretion, like that of epinephrine, involves the activation of luminal surface Na+ channels, whereas the inhibitory effect of asphyxia does not.

Ursodeoxycholic acid inhibits glucagon-induced cAMP formation in hamster hepatocytes: a role for PKC

1995 ◽  
Vol 268 (2) ◽  
pp. G300-G310 ◽  
Author(s):  
B. Bouscarel ◽  
T. W. Gettys ◽  
H. Fromm ◽  
H. Dubner
Keyword(s):  
Ursodeoxycholic Acid ◽  
Bile Acids ◽  
Inhibitory Effect ◽  
Camp Production ◽  
Glucagon Receptor ◽  
Pkc Inhibitor ◽  
Camp Synthesis ◽  
Kinase C ◽  
Camp Formation ◽  
Pkc Activation

The effect of bile acids on adenosine 3',5'-cyclic monophosphate (cAMP) synthesis was investigated in isolated hamster hepatocytes. Bile acids had no direct effect on cAMP production. However, ursodeoxycholic acid (UDCA) and tauroursodeoxycholic acid inhibited, by approximately 45%, cAMP formation induced by concentrations of glucagon greater than 1 nM, with a respective half-maximum inhibitory effect observed at 4 +/- 2 microM. Similar inhibition was observed with phorbol 12-myristate 13-acetate (PMA). Chenodeoxycholic, murocholic, and taurodeoxycholic acids were the next most potent bile acids. Taurolithocholic acid was 100-fold less potent than UDCA, whereas both ursocholic and taurocholic acids had no effect at concentrations up to 0.5 mM. Neither bile acids nor PMA affected either the binding of glucagon to its receptor, the cAMP-dependent phosphodiesterase, adenylate cyclase, or the inhibitory and stimulatory (Gs) GTP-binding proteins. The inhibitory effect of PMA and UDCA on glucagon-induced cAMP synthesis was abolished in the presence of the protein kinase C (PKC) inhibitor, staurosporine. Furthermore, UDCA induced PKC translocation from cytosol to membrane and stimulated phosphorylation of an 80-kDa protein substrate for PKC. In conclusion, mediated by PKC activation, bile acids inhibit glucagon-induced cAMP synthesis by uncoupling the glucagon receptor and Gs.

Evidence that separate PGE2 receptors modulate water and sodium transport in rabbit cortical collecting duct

1993 ◽  
Vol 265 (5) ◽  
pp. F643-F650 ◽  
Author(s):  
R. L. Hebert ◽  
H. R. Jacobson ◽  
D. Fredin ◽  
M. D. Breyer
Keyword(s):  
Pertussis Toxin ◽  
Water Permeability ◽  
Sodium Transport ◽  
Collecting Duct ◽  
Inhibitory Effect ◽  
Cortical Collecting Duct ◽  
Pkc Inhibitor ◽  
Kinase C ◽  
Pge2 Receptor ◽  
Pkc Activation

Prostaglandin E2 (PGE2) modulates both water and sodium transport in the rabbit cortical collecting duct (CCD). To determine whether these effects are mediated by separate PGE2 receptors, we compared the effects of PGE2 and its analogue sulprostone in the isolated perfused rabbit CCD. PGE2 increased basal water permeability (hydraulic conductivity), whereas sulprostone did not. PGE2 and sulprostone were equipotent inhibitors of water absorption when it was prestimulated by vasopressin. Pertussis toxin completely reversed the inhibitory effect of sulprostone but only partially reversed the inhibitory effect of PGE2. In contrast, a protein kinase C (PKC) inhibitor, staurosporine, partially reversed the inhibitory effect of PGE2 but had no effect on sulprostone. PGE2 also raised intracellular calcium ([Ca2+]i). This effect is coupled to its capacity to inhibit Na+ absorption. Sulprostone was 10-fold less potent than PGE2 both in raising [Ca2+]i or inhibiting sodium transport. The results suggest sulprostone selectively interacts with a PGE2 receptor coupled to pertussis toxin-sensitive inhibition of water permeability. Sulprostone less potently activates a PGE2 receptor coupled to [Ca2+]i, PKC activation, and sodium transport and completely fails to interact with the PGE2 receptor that stimulates water permeability in the collecting duct. These results suggest distinct PGE2 receptors modulate sodium and water transport in the CCD.

scholarly journals Androgens and Postmeiotic Germ Cells Regulate Claudin-11 Expression in Rat Sertoli Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1532-1540 ◽  
Author(s):  
Anne Florin ◽  
Magali Maire ◽  
Aline Bozec ◽  
Ali Hellani ◽  
Sonia Chater ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Adult Age ◽  
Adult Rat ◽  
Protein Levels ◽  
Negative Effect

In the present study we investigated whether fetal exposure to flutamide affected messenger and protein levels of claudin-11, a key Sertoli cell factor in the establishment of the hemotesticular barrier, at the time of two key events of postnatal testis development: 1) before puberty (postnatal d 14) during the establishment of the hemotesticular barrier, and 2) at the adult age (postnatal d 90) at the time of full spermatogenesis. The data obtained show that claudin-11 expression was inhibited in prepubertal rat testes exposed in utero to 2 and 10 mg/kg·d flutamide. However, in adult testes, the inhibition was observed only with 2, and not with 10, mg/kg·d of the antiandrogen. It is shown here that these differences between prepubertal and adult testes could be related to dual and opposed regulation of claudin-11 expression resulting from positive control by androgens and an inhibitory effect of postmeiotic germ cells. Indeed, testosterone is shown to stimulate claudin-11 expression in cultured Sertoli cells in a dose- and time-dependent manner (maximum effect with 0.06 μm after 72 h of treatment). In contrast, postmeiotic germ cells potentially exert a negative effect on claudin-11 expression, because adult rat testes depleted in spermatids (after local irradiation) displayed increased claudin-11 expression, whereas in a model of cocultured Sertoli and germ cells, spermatids, but not spermatocytes, inhibited claudin-11 expression. The apparent absence of claudin-11 expression changes in adult rat testes exposed to 10 mg/kg·d flutamide therefore could result from the antagonistic effects of 1) the inhibitory action of the antiandrogen and 2) the stimulatory effect of the apoptotic germ cells on claudin-11 expression. Together, due to the key role of claudin-11 in the hemotesticular barrier, the present findings suggest that such regulatory mechanisms may potentially affect this barrier (re)modeling during spermatogenesis.

Intramembranous absorption rate is unaffected by changes in amniotic fluid composition

2005 ◽  
Vol 288 (5) ◽  
pp. F964-F968 ◽  
Author(s):  
D. Anderson ◽  
Q. Yang ◽  
A. Hohimer ◽  
J. Faber ◽  
G. Giraud ◽  
...  
Keyword(s):  
Amniotic Fluid ◽  
Flow Measurement ◽  
Control Period ◽  
Ringer Solution ◽  
Urine Flow ◽  
Fluid Composition ◽  
Fetal Sheep ◽  
Urine Production ◽  
Blood Pressures ◽  
Vascular Catheters

Experiments were performed to determine the effect of amniotic fluid dilution on the rate of intramembranous absorption. Seven fetal sheep at 118 days gestation were instrumented with a shunt between the trachea and esophagus and arterial and venous vascular catheters. In addition, the urachus of the fetal bladder was ligated, and a catheter was placed in the bladder. Ligation of the urachus does not interfere with urine flow into the amnion. After 5 days of recovery, fetuses were randomly assigned to one of two protocols; all fetuses completed both protocols. In the fetuses in the control period, continuous urine flow measurement was begun. In the fetuses assigned to the isovolumic dilution protocol, continuous urine flow measurement was also begun and, in addition, amniotic fluid was continually exchanged with lactated Ringer solution on an isovolumic basis. After 3–4 days, fetal blood pressures and amniotic fluid volumes were determined. Amniotic fluid volumes were determined by drainage. Each fetus was then assigned to the remaining protocol. The presence of the tracheal-esophageal shunt and the ligation of the urachus allowed the rate of intramembranous absorption to be calculated. Isovolumic exchange showed no effect on fetal vascular pressures, blood-gas values, or urine production. We could demonstrate no effect of isovolumic dilution of amniotic fluid on its volume. However, we were able to demonstrate an inverse relationship between amniotic fluid volume and intramembranous absorption ( P < 0.02).

scholarly journals Studies on the interaction of growth regulators with potassium ions in some physiological processes in bean (Phaseolus vulgaris L.). III The effect of growth regulators on growth, chlorophyll level and transpiration depending on potassium concentration

2014 ◽  
Vol 55 (4) ◽  
pp. 577-588
Author(s):  
Jadwiga Stopińska
Keyword(s):  
Growth Regulators ◽  
Potassium Concentration ◽  
Leaf Growth ◽  
Inhibitory Effect ◽  
Physiological Effect ◽  
Potassium Ions ◽  
Phaseolus Vulgaris L ◽  
Physiological Processes ◽  
Bean Plants ◽  
Chlorophyll Level

Leaf growth and chlorophyll level in GA<sub>3</sub>-treated bean, and leaf growth and transpiration intensity in ABA-treated bean plants were studied at two potassium concentrations in the medium (1 and 3 mM KNO<sub>3</sub>). The plants were grown on Hoagland's solution and growth regulators were applied to the shoot growth apexes. Both GA<sub>3</sub> and K<sup>+</sup> ions were found to stimulate growth of primary leaves and increase their potassium amount. GA<sub>3</sub> contrary to K<sup>+</sup> slightly decreased the potassium content in leaves Both factors reduced the chlorophyll content but did not affect the total chlorophyll amount in these organs Interaction between GA<sub>3</sub> and K<sup>+</sup> ions was of additive nature. The effect of ABA and K<sup>+</sup> ions on growth of both kinds of leaves and on the amount and content of potassium in them were antagonistic. The inhibitory effect of the hormone was stronger at higher potassium concentration in the medium. Either factor reduced transpiration intensity in leaves, however, the inhibitory effect of the growth regulator was stronger at lower potassium concentration. The potassium level modified both the physiological effect of the regulators and the sensitivity of bean particularly to ABA.

scholarly journals Effect of tryptophan on the early tri-iodothyronine uptake in mouse thymocytes

2000 ◽  
pp. 119-123 ◽  
Author(s):  
M Centanni ◽  
G Canettieri ◽  
N Viceconti ◽  
R Sibilla ◽  
A Bei ◽  
...  
Keyword(s):  
Initial Rate ◽  
Inhibitory Effect ◽  
Ringer Solution ◽  
Sodium Depletion ◽  
Independent Components ◽  
Competitive Mechanism ◽  
Sodium Dependent ◽  
In Cis ◽  
Competitive Nature ◽  
Dose Dependent

OBJECTIVE: We have studied the effect of tryptophan on cellular [(125)I]tri-iodothyronine (T3) uptake by mouse thymocytes. MATERIALS AND METHODS: Mouse thymocytes (20 x 10(6 )cells/ml) were suspended in Krebs-Ringer solution buffered by Tris-HCl and incubation (23 degrees C at pH7.45+/-0.6), in the presence or absence of 1mM tryptophan, was started by adding 25 pM [(125)I]T3. At the end of incubation, samples were cooled in ice, centrifuged over a 30% sucrose cushion and the cell-associated radioactivity was measured in the pellet. RESULTS: Tryptophan reduced both the total and the saturable fraction of [(125)I]T3 uptake by 44% (P=0.0009) and 60% (P=0.0006) respectively, following 1 min of incubation. This effect was specific and dose-dependent, being maximal at 5mM concentration (-82%). In contrast, the pre-exposure of cells to tryptophan for up to 2h had no effect on the subsequent uptake of [(125)I]T3, in the absence of tryptophan. The effect of D-tryptophan on saturable T3 uptake was not different from that obtained using the L-stereoisomer. Tryptophan reduced the V(max) of the initial rate of saturable [(125)I]T3 uptake by two-thirds without affecting the apparent K(m) (2.2 nM) of the process, thus indicating the non-competitive nature of the inhibition. In sodium-free medium the saturable [(125)I]T3 uptake was reduced by 43%. The inhibitory effect of tryptophan on [(125)I]T3 uptake was exerted in both the presence and the absence of sodium. In fact, the inhibitory effect of tryptophan on T3 transport was greater and significantly different (P=0.0046) from that obtained by sodium depletion alone. CONCLUSIONS: Tryptophan interferes with both the sodium-dependent and -independent components of [(125)I]T3 uptake by a dose-dependent, non-competitive mechanism which operates in cis-modality at the plasma membrane level of mouse thymocytes.

GHRF causes biphasic stimulation of SRIF secretion from rat hypothalamic cells

1988 ◽  
Vol 255 (6) ◽  
pp. E829-E832
Author(s):  
S. Richardson ◽  
S. Twente ◽  
T. Audhya
Keyword(s):  
Response Curve ◽  
Response Pattern ◽  
Cell Function ◽  
Physiological Regulation ◽  
Gh Secretion ◽  
Adult Rat ◽  
Complex Interactions ◽  
Hypothalamic Cells ◽  
Dose Dependent ◽  
Stimulation Of

The complex interactions of the hypothalamic releasing peptides somatostatin (SRIF) and growth hormone (GH)-releasing hormone (GHRF), which regulate GH secretion, are still incompletely understood. To further scrutinize these interactions, we have studied the effects of GHRF on SRIF secretion from dispersed adult rat hypothalamic cells. Rat GHRF caused calcium- and dose-dependent stimulation of SRIF release in static 1-h incubations. SRIF release was stimulated by GHRF in a concentration range of 1-100 nM. However, the extended dose-response curve was biphasic in nature, with a significantly lower SRIF response in the presence of 1 microM GHRF vs. 100 nM GHRF. SRIF release, stimulated by another secretagogue (10 microM veratridine), was not affected by the presence or absence of 1 microM GHRF, suggesting the lack of toxic impairment of hypothalamic cell function by GHRF at this concentration. In conclusion, a biphasic stimulatory pattern of SRIF secretion in response to GHRF was observed in experiments employing dispersed rat hypothalamic cells. The biphasic SRIF response pattern to GHRF may be relevant in the physiological regulation of GH secretion.

Inhibitory effect of ethacrynic acid on chloride permeability

1976 ◽  
Vol 231 (5) ◽  
pp. 1485-1489 ◽  
Author(s):  
R Motais ◽  
JL Cousin
Keyword(s):  
Hydrophobic Interaction ◽  
Ethacrynic Acid ◽  
Chloride Transport ◽  
Direct Proof ◽  
Inhibitory Effect ◽  
Ringer Solution ◽  
Relative Activity ◽  
Chloride Permeability ◽  
Sh Group ◽  
Highly Correlated

Ethacrynic acid inhibits anion movements in ox red blood cells. The I50 for chloride is 7 X 10(-6) M. The inhibitory effect is instantaneous and completely reversed by washing the cells with a Ringer solution, suggesting that reaction with a membrane SH group is not involved in this process. Direct proof that ethacrynic acid does not act by its reactivity with thiol groups is given by experiments with dihydroethacrynic acid, a derivative that lacks the ability to combine with SH groups: the characteristics of inhibition are strictly identical (instantaneous and reversible; I50 equals 9 X 10(-6) M). All the phenoxyacetic derivatives tested were also more or less inhibitory. The relative activity of all the derivatives was highly correlated with their liposolubility, indicating that hydrophobic interaction is important in determining drug effect and influence of steric factors is minimal. The data suggest that inhibition essentially results from a hydrophobic interaction between ethacrynic acid and apolar regions of the membrane protein allowing chloride transport.

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