scholarly journals Induction of renal arachidonate cytochrome P-450 epoxygenase after uninephrectomy: counterregulation of hyperfiltration.

1993 ◽  
Vol 3 (8) ◽  
pp. 1496-1500
Author(s):  
K Takahashi ◽  
R C Harris ◽  
J H Capdevila ◽  
A Karara ◽  
K Makita ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Enzymatic Activity ◽  
Renal Mass ◽  
Rat Kidney ◽  
Unilateral Nephrectomy ◽  
Arachidonate Metabolism ◽  
Baseline Values ◽  
Cytochrome P 450 ◽  
Stimulation Of

After unilateral nephrectomy (UNx) in the rat, cytochrome P-450 (cP-450)-linked arachidonate enzymatic activity was markedly and specifically induced in microsomal fractions from the remaining kidney. The enzymatic activity reached 200% at 1 wk and 285% at 2 wk post-UNx as compared with non-UNx controls. Mean baseline values for GFR and RPF rate in the remaining kidney 2 wk after UNx were 1.56 +/- 0.10 and 6.47 +/- 0.35 mL/min, respectively. In these rats, the administration of ketoconazole, a cP-450 inhibitor, led to 75% inhibition of renal cP-450 arachidonate metabolism and was associated with acute augmentations in both GFR and RPF to 1.82 +/- 0.18 (P < 0.05 versus baseline) and 7.54 +/- 0.37 mL/min (P < 0.05 versus baseline), respectively. Because vasoconstrictor arachidonate epoxygenase products are endogenously generated in the rat kidney, these findings suggest that the stimulation of renal cP-450-mediated oxygenation of arachidonic acid may subserve an important counterregulatory function in mitigating the renal hyperperfusion and hyperfiltration that follow reductions in renal mass.

Cytochrome P-450-dependent vasodilation of rat kidney by arachidonic acid

1991 ◽  
Vol 261 (3) ◽  
pp. H714-H719 ◽  
Author(s):  
A. O. Oyekan ◽  
J. C. McGiff ◽  
J. Quilley
Keyword(s):  
Arachidonic Acid ◽  
Cobalt Chloride ◽  
Stannous Chloride ◽  
Rat Kidney ◽  
Vasodilator Effect ◽  
Vasodilator Response ◽  
Cytochrome P 450 ◽  
Experimental Preparation ◽  
In Vivo Induction

Our previous studies indicated a role for cytochrome P-450-dependent enzymes in generating the mediators of the vasodilator effect of arachidonic acid (AA) in the preconstricted indomethacin-treated perfused kidney of the rat. We report that in vivo induction of cytochrome P-450 enzymes with 3-methylcholanthrene-beta-naphthoflavone or dexamethasone enhanced the renal vasodilator effect of AA in this experimental preparation. Conversely, depletion of cytochrome P-450 enzymes with stannous chloride or cobalt chloride diminished the vasodilator response to AA. Injection of AA resulted in the release of relaxant material into the renal effluent detected by superfusion of rabbit aortic rings. Inhibition of cytochrome P-450 with 7-ethoxyresorufin reduced the release of vasorelaxant material. Metabolism of labeled AA by the kidney revealed four peaks of radioactivity that were recovered from the renal effluent. The heights of these peaks were reduced by 7-ethoxyresorufin. These results provide further evidence for cytochrome P-450-dependent metabolism of AA to one or more vasodilator products by the rat kidney.

A role for G-proteins in the epidermal growth factor stimulation of phospholipase A2 in rat kidney mesangial cells

1990 ◽  
Vol 10 (4) ◽  
pp. 353-362 ◽  
Author(s):  
Nashrudeen Hack ◽  
Paula Clayman ◽  
Karl Skorecki
Keyword(s):  
Arachidonic Acid ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Phospholipase A2 ◽  
G Protein ◽  
Mesangial Cells ◽  
Rat Kidney ◽  
Glomerular Mesangial Cells ◽  
Epidermal Growth ◽  
Stimulation Of

We have previously demonstrated phospholipase C (PLC) independent activation of phospholipase A2(PLA2) by epidermal growth factor (EGF) in glomerular mesangial cells in culture. In the current study using glass beads to permeabilize [3H]- or [14C]-arachidonate labelled mesangial cells we demonstrate that guanine nucleotides modulate the EGF-mediated stimulation of arachidonic acid release (75% inhibition with 100 μM GDPβS and 108% augmentation with 100 μM GTPγS). GTPγS alone stimulated both the release of free arachidonic acid and production of diacylglycerol (DAG), while EGF itself neither stimulated DAG nor augmented the DAG response to GTPγS. These findings suggest the intermediacy of a G-protein in PLC-independent stimulation of PLA2 by a growth factor, and provide a model system for determining the relationship between G-protein intermediacy and the intrinsic tyrosine kinase activity of the growth factor receptor.

scholarly journals Arachidonic acid inhibits basolateral K channels in the cortical collecting duct via cytochrome P-450 epoxygenase-dependent metabolic pathways

2008 ◽  
Vol 294 (6) ◽  
pp. F1441-F1447 ◽  
Author(s):  
ZhiJian Wang ◽  
Yuan Wei ◽  
John R. Falck ◽  
Krishnam Raju Atcha ◽  
Wen-Hui Wang
Keyword(s):  
Arachidonic Acid ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Inhibitory Effect ◽  
K Channel ◽  
Dependent Manner ◽  
Cortical Collecting Duct ◽  
Patch Clamp Technique ◽  
K Channels ◽  
Cytochrome P 450

We used the patch-clamp technique to study the effect of arachidonic acid (AA) on basolateral 18-pS K channels in the principal cell of the cortical collecting duct (CCD) of the rat kidney. Application of AA inhibited the 18-pS K channels in a dose-dependent manner and 10 μM AA caused a maximal inhibition. The effect of AA on the 18-pS K channel was specific because application of 11,14,17-eicosatrienoic acid had no effect on channel activity. Also, the inhibitory effect of AA on the 18-pS K channels was abolished by blocking cytochrome P-450 (CYP) epoxygenase with N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide (MS-PPOH) but was not affected by inhibiting CYP ω-hydroxylase or cyclooxygenase. The notion that the inhibitory effect of AA was mediated by CYP epoxygenase-dependent metabolites was further supported by the observation that application of 100 nM 11,12-epoxyeicosatrienoic acid (EET) mimicked the effect of AA and inhibited the basolateral 18-pS K channels. In contrast, addition of either 5,6-, 8,9-, or 14,15-EET failed to inhibit the 18-pS K channels. Moreover, application of 11,12-EET was still able to inhibit the 18-pS K channels in the presence of MS-PPOH. This suggests that 11,12-EET is a mediator for the AA-induced inhibition of the 18-pS K channels. We conclude that AA inhibits basolateral 18-pS K channels by a CYP epoxygenase-dependent pathway and that 11,12-EET is a mediator for the effect of AA on basolateral K channels in the CCD.

scholarly journals Inositol lipid signalling occurs in brush-border membranes during initiation of compensatory renal growth in the rat

1993 ◽  
Vol 295 (2) ◽  
pp. 599-605 ◽  
Author(s):  
H Banfić ◽  
M Vuica ◽  
M Knotek ◽  
S Moslavac ◽  
N Divecha
Keyword(s):  
Brush Border ◽  
Plasma Membranes ◽  
Rat Kidney ◽  
Unilateral Nephrectomy ◽  
Kidney Cortex ◽  
Compensatory Renal Growth ◽  
Rat Kidney Cortex ◽  
Contralateral Kidney ◽  
Inositol Lipids ◽  
Stimulation Of

Using highly specific mass assays, concentrations of inositol lipids and 1,2-diacylglycerol (DAG) were determined in plasma membranes isolated from rat kidney cortex. Significantly higher concentrations of inositol lipids were determined in brush-border (BBM) than in basal-lateral (BLM) plasma membranes, although DAG concentrations were similar in both. After unilateral nephrectomy, a decrease in PtdIns(4,5)P2 and PtdIns4P, with a concomitant increase in DAG and translocation of protein kinase C (PKC), were observed in BBM but not in BLM isolated from the remaining kidney. On the other hand, stimulation of renal cortical slices with insulin-like growth factor II (IGF-II) or phenylephrine caused similar effects in BLM but not in BBM. Stimulation of phospholipase C activity with translocation of PKC only to BBM in one kidney was also induced by occlusion of blood flow through the contralateral kidney for 15 min. At 30 min after the occlusion was removed and reflow established, DAG concentration and the amount of PKC in BBM returned to control values. These results suggest that an early signal after unilateral nephrectomy is transmitted to cells through BBM and can be switched on and off by blood occlusion and reflow through the contralateral kidney, while hormonal signals caused by IGF-II and phenylephrine are transmitted to cells through BLM.

Adenosine inhibits ENaC via cytochrome P-450 epoxygenase-dependent metabolites of arachidonic acid

2006 ◽  
Vol 290 (5) ◽  
pp. F1163-F1168 ◽  
Author(s):  
Yuan Wei ◽  
Peng Sun ◽  
ZhiJian Wang ◽  
BaoFeng Yang ◽  
Mairead A. Carroll ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Adenosine Receptor ◽  
Receptor Agonist ◽  
Inhibitory Effect ◽  
Channel Activity ◽  
Patch Clamp Technique ◽  
Adenosine Receptor Agonist ◽  
Cytochrome P 450 ◽  
Stimulation Of

We used the patch-clamp technique to examine the effect of adenosine on epithelial sodium channel (ENaC) activity in rat cortical collecting duct (CCD). Application of adenosine inhibits ENaC activity, and the effect of adenosine was mimicked by cyclohexyladenosine (CHA), an A1 adenosine-receptor agonist that reduced channel activity from 1.32 to 0.64. The inhibitory effect of CHA on ENaC was mimicked by cyclopentyladenosine (CPA), which reduced channel activity from 1.1 to 0.55. In contrast, application of CGS-21680, an A2a adenosine-receptor agonist, had no effect on ENaC and increased channel activity from 0.96 to 1.22. This suggests that the inhibitory effect of adenosine analogs resulted from stimulation of the A1 adenosine receptor. Inhibition of PLC with U-73122 failed to abolish the effect of CHA on ENaC. In contrast, the inhibitory effect of CHA on ENaC was absent in the presence of the PLA2 inhibitor arachidonyl trifluoromethyl ketone (AACOCF3). This suggests a role of arachidonic acid (AA) in mediating the effect of adenosine on ENaC. To determine the metabolic pathway of AA responsible for the effect of adenosine, we examined the effect of CHA in the presence of indomethacin or N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide (MS-PPOH). Inhibition of cytochrome P-450 (CYP) epoxygenase with MS-PPOH blocked the effect of CHA on ENaC. In contrast, CHA reduced ENaC activity in the presence of indomethacin. This suggests that CYP epoxygenase-dependent metabolites of AA mediate the effect of adenosine. Because 11,12-epoxyeicosatrienoic acid (11,12-EET) inhibits ENaC activity in the CCD (Wei Y, Lin DH, Kemp R, Yaddanapudi GSS, Nasjletti A, Falck JR, and Wang WH. J Gen Physiol 124: 719–727, 2004), we examined the role of 11,12-EET in mediating the effect of adenosine on ENaC. Addition of 11,12-EET inhibited ENaC channels in the CCD in which adenosine-induced inhibition was blocked by AACOCF3. We conclude that adenosine inhibits ENaC activity by stimulation of the A1 adenosine receptor in the CCD and that the effect of adenosine is mediated by 11,12-EET.

Na(+)-K+(NH4+)-2Cl- cotransport in medullary thick ascending limb: control by PKA, PKC, and 20-HETE

1996 ◽  
Vol 271 (2) ◽  
pp. C455-C463 ◽  
Author(s):  
H. Amlal ◽  
C. Legoff ◽  
C. Vernimmen ◽  
M. Paillard ◽  
M. Bichara
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Rat Kidney ◽  
Thick Ascending Limb ◽  
Dependent Protein Kinase ◽  
Cyclic Monophosphate ◽  
Medullary Thick Ascending Limb ◽  
Kinase C ◽  
Dependent Protein ◽  
Cytochrome P 450

Cell pH was monitored in suspensions of medullary thick ascending limbs (MTALs) of rat kidney to determine possible effects of various transduction pathways on apical Na(+)-K+ (NH4+)-2Cl- cotransport, the activity of which was measured as the bumetanide-sensitive component of cell acidification caused by abrupt exposure to 4 mM NH4Cl. 8-Bromoadenosine 3',5'-cyclic monophosphate stimulated cotransport activity through activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA), since the cAMP effect was abolished by N-[2-(p- bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89); stimulation by cAMP (P < 0.02) was observed even when other Na+, Cl-, and K+ carriers were blocked by ouabain, diphenylamine-2-carboxylate, and barium, which indicates that cotransport was directly affected by PKA. Phorbol 12,13-dibutyrate also stimulated cotransport activity (P < 0.03), which was abolished by protein kinase C (PKC) blockade by staurosporine. In contrast, cotransport activity was reduced (P < 0.001) by arachidonic acid or 20-hydroxyeicosatetraenoic acid (20-HETE), as well as by an ionomycin-induced rise in cytosolic Ca2+ ([Ca2+]i). Inhibition by arachidonic acid or ionomycin was abolished by econazole and SKF-525A that inhibit cytochrome P-450-dependent monoxygenase, which produces 20-HETE from arachidonic acid in the MTAL, and the ionomycin effect was prevented when phospholipase A2 (PLA2) was blocked by 4-bromophenacyl bromide or oleyloxyethyl phosphorylcholine. The results demonstrate that MTAL apical Na(+)-K+(NH4+)-2Cl- cotransport is stimulated by PKA and PKC and inhibited by 20-HETE that may be produced after a rise in [Ca2+]i through PLA2 activation.

scholarly journals Molecular cloning, expression, and enzymatic characterization of the rat kidney cytochrome P-450 arachidonic acid epoxygenase

1993 ◽  
Vol 268 (18) ◽  
pp. 13565-13570
Author(s):  
A. Karara ◽  
K. Makita ◽  
H.R. Jacobson ◽  
J.R. Falck ◽  
F.P. Guengerich ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Molecular Cloning ◽  
Rat Kidney ◽  
Enzymatic Characterization ◽  
Cytochrome P 450

Stimulated Platelet Aggregation, Thromboxane B2 Formation and Platelet Sensitivity to Prostacyclin - A Critical Evaluation

1981 ◽  
Vol 45 (03) ◽  
pp. 204-207 ◽  
Author(s):  
Wolfgang Siess ◽  
Peter Roth ◽  
Peter C Weber
Keyword(s):  
Arachidonic Acid ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Reliable Method ◽  
Platelet Rich Plasma ◽  
Critical Evaluation ◽  
Vascular Diseases ◽  
Thromboxane B2 ◽  
Test Time ◽  
Stimulation Of

SummaryPlatelets have been implicated in the development of atherosclerotic and thrombotic vascular diseases. Evaluation of platelet aggregation in relation to endogenously formed compounds which affect platelet function may provide information of clinical and pharmacological relevance. We describe a method in which thromboxane B2 (TXB2) formation was analyzed following stimulation of platelet-rich plasma (PRP) with ADP, 1-epinephrine, collagen, and arachidonic acid. In addition, we determined platelet sensitivity to prostacyclin following ADP- and collagen-induced platelet aggregation. The parameters under study were found to depend on the platelet count in PRP, on the type and dose of the aggregating agent used, and on the test time after blood sampling. By standardization of these variables, a reliable method was established which can be used in clinical and pharmacological trials.

Isolation of Antithrombin III from Normal and α1-Antitrypsin-Deficient Human Plasma

1977 ◽  
Vol 38 (02) ◽  
pp. 0475-0485 ◽  
Author(s):  
Anna D. Borsodi ◽  
Ralph A. Bradshaw
Keyword(s):  
Enzymatic Activity ◽  
Isoelectric Focusing ◽  
Antithrombin Iii ◽  
Factor Xa ◽  
Antithrombin Activity ◽  
Bovine Trypsin ◽  
Normal Plasma ◽  
Antitrypsin Deficiency ◽  
Simplified Procedure ◽  
Stimulation Of

SummaryThe plasma of individuals, hetero- or homozygous for α1-antitrypsin deficiency, contains greatly decreased amounts of antithrombin activity as assayed against factor Xa. However, heparin stimulation of the residual antithrombin activity is observed, which is comparable to that of normal plasma. Antithrombins isolated from both normal and α1-antitrypsin deficient plasma by a simplified procedure are indistinguishable in both properties and yields. The microheterogeneity observed on isoelectric focusing of both preparations can be eliminated by treatment with neuraminidase. Neither purified human antithrombin nor α1-antitrypsin, when assayed against bovine trypsin, is stimulated by heparin. These results clearly establish the unique natures of antithrombin and α1-antitrypsin and show that about 75% of the antithrombin activity measured in normal plasma is due to α1-antitrypsin. Estimates of anti thrombin III activity in normal plasma by assays dependent on enzymatic activity can probably be obtained only in the presence of heparin.

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