scholarly journals Arachidonic acid (AA) inhibits basolateral K channels in the cortical collecting duct (CCD) via cytochrome P450 (CYP) epoxygenase‐dependent metabolic pathways

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Zhijian Wang ◽  
Yuan Wei ◽  
Wenhui Wang
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Metabolic Pathways ◽  
Collecting Duct ◽  
Cortical Collecting Duct ◽  
K Channels

scholarly journals Arachidonic Acid Inhibits Epithelial Na Channel Via Cytochrome P450 (CYP) Epoxygenase-dependent Metabolic Pathways

2004 ◽  
Vol 124 (6) ◽  
pp. 719-727 ◽  
Author(s):  
Yuan Wei ◽  
Dao-Hong Lin ◽  
Rowena Kemp ◽  
Ganesh S.S. Yaddanapudi ◽  
Alberto Nasjletti ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Collecting Duct ◽  
Inhibitory Effect ◽  
Mass Spectrometry Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
Na Channel ◽  
Cortical Collecting Duct ◽  
Patch Clamp Technique ◽  
Spectrometry Analysis

We used the patch-clamp technique to study the effect of arachidonic acid (AA) on epithelial Na channels (ENaC) in the rat cortical collecting duct (CCD). Application of 10 μM AA decreased the ENaC activity defined by NPo from 1.0 to 0.1. The dose–response curve of the AA effect on ENaC shows that 2 μM AA inhibited the ENaC activity by 50%. The effect of AA on ENaC is specific because neither 5,8,11,14-eicosatetraynoic acid (ETYA), a nonmetabolized analogue of AA, nor 11,14,17-eicosatrienoic acid mimicked the inhibitory effect of AA on ENaC. Moreover, inhibition of either cyclooxygenase (COX) with indomethacin or cytochrome P450 (CYP) ω-hydroxylation with N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) failed to abolish the effect of AA on ENaC. In contrast, the inhibitory effect of AA on ENaC was absent in the presence of N-methylsulfonyl-6-(propargyloxyphenyl)hexanamide (MS-PPOH), an agent that inhibits CYP-epoxygenase activity. The notion that the inhibitory effect of AA is mediated by CYP-epoxygenase–dependent metabolites is also supported by the observation that application of 200 nM 11,12-epoxyeicosatrienoic acid (EET) inhibited ENaC in the CCD. In contrast, addition of 5,6-, 8,9-, or 14,15-EET failed to decrease ENaC activity. Also, application of 11,12-EET can still reduce ENaC activity in the presence of MS-PPOH, suggesting that 11,12-EET is a mediator for the AA-induced inhibition of ENaC. Furthermore, gas chromatography mass spectrometry analysis detected the presence of 11,12-EET in the CCD and CYP2C23 is expressed in the principal cells of the CCD. We conclude that AA inhibits ENaC activity in the CCD and that the effect of AA is mediated by a CYP-epoxygenase–dependent metabolite, 11,12-EET.

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.

A role for PKCε and MAP kinase in bradykinin-induced arachidonic acid release in rabbit CCD cells

1998 ◽  
Vol 274 (4) ◽  
pp. F728-F735 ◽  
Author(s):  
Mark A. Lal ◽  
Pierre R. Proulx ◽  
Richard L. Hébert
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Intracellular Signaling ◽  
Collecting Duct ◽  
Mitogen Activated Protein Kinase ◽  
Cortical Collecting Duct ◽  
Paracrine Factors ◽  
Mapk Activation ◽  
Rate Limiting Step ◽  
Mitogen Activated Protein

Arachidonic acid (AA) release is the rate-limiting step in the production of prostaglandins, an important class of autocrine/paracrine factors that modulate collecting duct function. Previous results from this laboratory have established cytosolic phospholipase A2(cPLA2) as the enzyme responsible for bradykinin (BK)-stimulated AA mobilization in rabbit cortical collecting duct (RCCD) cells, and the present study pursues the intracellular signaling mechanisms responsible for its activation. Pretreatment of cells with Ro-31-8220, an inhibitor of protein kinase C (PKC), or PD-98059, an inhibitor of the mitogen-activated protein kinase (MAPK) cascade, resulted in a 50–60% reduction in BK-stimulated AA release. Incubation of RCCD cells with a combination of both Ro-31-8220 and PD-98059 did not achieve a greater inhibition of either BK-stimulated AA release or cPLA2 activity, possibly indicating that MAPK activation was dependent upon prior activation of PKC. This was supported by the observation that BK-induced MAPK activation could be reversed by either inhibitor. Additional experiments dealing with immunoblots for PKC isozymes revealed that RCCD cells express PKC species α, γ, ε, and ζ. Following BK stimulation, only PKCε translocated to the particulate fraction. Based on these results, it appears that PKC is activated and involved in the sequential activation of MAPK and cPLA2 following BK treatment. The results also suggest that PKCε may be the isozyme implicated in the process.

Different mechanisms of renal Na-K-ATPase regulation by protein kinases in proximal and distal nephron

1993 ◽  
Vol 265 (3) ◽  
pp. F399-F405 ◽  
Author(s):  
T. Satoh ◽  
H. T. Cohen ◽  
A. I. Katz
Keyword(s):  
Arachidonic Acid ◽  
Protein Kinase ◽  
Collecting Duct ◽  
Common Mechanism ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Distal Nephron ◽  
Inhibitory Peptide ◽  
Medullary Thick Ascending Limb ◽  
Pump Activity

We recently reported a novel intracellular mechanism of Na-K-adenosinetriphosphatase (Na-K-ATPase) regulation in the cortical collecting duct (CCD) by agents that increase cell adenosine 3',5'-cyclic monophosphate (cAMP), which involves stimulation of protein kinase A (PKA) and phospholipase A2 (PLA2). We now determined whether this mechanism also operates in other nephron segments. In the medullary thick ascending limb (MTAL) dopamine, the DA1 agonist fenoldopam, forskolin, or dibutyryl-cAMP inhibited Na-K-ATPase activity, similar to results in CCD. In both segments this effect was blocked by 20-residue inhibitory peptide (IP20), a peptide inhibitor of PKA, but not by staurosporine, a protein kinase C (PKC) inhibitor. PKC activators phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate, and 1,2-myristate 13-acetate, phorbol 12,13-dibutyrate, and 1,2-dioctanoylglycerol had no effect on Na-K pump activity in either CCD or MTAL. In contrast, all three PKC activators inhibited pump activity in the proximal convoluted tubule (PCT), an effect reproduced only by dopamine or by parathyroid hormone [PTH-(1-34)]. In PCT the pump inhibition by dopamine or PTH-(1-34) was abolished by staurosporine but not by IP20. The PLA2 inhibitor mepacrine prevented the effect of all agents, and arachidonic acid produced a dose-dependent pump inhibition in each of the three segments studied. We conclude that intracellular mechanisms of Na-K-ATPase regulation differ along the nephron, as they involve activation of PKA in CCD and MTAL and of PKC in PCT. These two pathways probably share a common mechanism in stimulating PLA2, arachidonic acid release, and production of eicosanoids in both the proximal and distal nephron.

scholarly journals Abnormal arachidonic acid metabolic network may reduce sperm motility via P38 MAPK

Open Biology ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 180091 ◽  
Author(s):  
Lisha Yu ◽  
Xiaojing Yang ◽  
Bo Ma ◽  
Hanjie Ying ◽  
Xuejun Shang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Metabolic Network ◽  
P38 Mapk ◽  
Sperm Motility ◽  
Seminal Plasma ◽  
Metabolic Pathways ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Activation

Asthenozoospermia is a common cause of male infertility, the aetiology of which remains unclear in 50–60% of cases. The current study aimed to characterize metabolic alterations in asthenozoospermic seminal plasma and to explore the signalling pathways involved in sperm motility regulation. At first, high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry was used to detect the targeted metabolic network of arachidonic acid (AA). Metabolomic multivariate data analysis showed significant distinction of AA metabolites between asthenozoospermic and healthy seminal plasma. AA as well as its lipoxygenase (LOX) and cytochrome P450 metabolites were found to be abnormally increased, while cyclooxygenase (COX) metabolites were complicatedly disturbed in asthenozoospermic volunteers compared with those in healthy ones. In vitro experiments and western blot analysis of sperm cells revealed a decrease in sperm motility and upregulation of sperm phosphor-P38 induced by AA. P38 inhibitor could increase AA-reduced sperm motility. Also, all the inhibitors of the three metabolic pathways of AA could block AA-induced P38 mitogen-activated protein kinase (MAPK) activation and further improve sperm motility. We report here for the first time that an abnormal AA metabolic network could reduce sperm motility via P38 MAPK activation through the LOX, cytochrome P450 and COX metabolic pathways, which might be an underlying pathomechanism of asthenozoospermia.

Arachidonic acid inhibits activity of cloned renal K+ channel, ROMK1

1996 ◽  
Vol 271 (3) ◽  
pp. F588-F594 ◽  
Author(s):  
C. M. Macica ◽  
Y. Yang ◽  
S. C. Hebert ◽  
W. H. Wang
Keyword(s):  
Arachidonic Acid ◽  
Membrane Fluidity ◽  
Collecting Duct ◽  
K Channel ◽  
Thick Ascending Limb ◽  
Cortical Collecting Duct ◽  
Channel Activity ◽  
Lipoxygenase Inhibitor ◽  
Open Probability ◽  
Apical Membranes

Arachidonic acid (AA) has been shown to inhibit the activity of the low-conductance ATP-sensitive K+ channel in the apical membrane of the cortical collecting duct [W. Wang, A. Cassola, and G. Giebisch. Am. J. Physiol. 262 (Renal Fluid Electrolyte Physiol. 31): F554-F559, 1992]. ROMK1, a K+ channel derived from the rat renal outer medulla, shares many biophysical properties of the native low-conductance K+ channel, which is localized to the apical membranes of the cortical collecting duct and thick ascending limb. This study was designed to determine whether the ROMK channel maintains the property of AA sensitivity of the native low-conductance K+ channel. Experiments were conducted in Xenopus oocytes injected with cRNA encoding the ROMK1 channel by use of patch-clamp techniques. We have confirmed previous reports that the cloned ROMK1 has similar channel kinetics, high open probability, and inward slope conductance as the native low-conductance K+ channel, respectively. Addition of 5 microM AA to an inside-out patch resulted in reversible inhibition of channel activity at a concentration similar to the inhibitor constant for AA on the native K+ channel. The effect of AA on channel activity was preserved in the presence of 10 microM indomethacin, a cyclooxygenase inhibitor, 4 microM cinnamyl-3,4-dihydroxycyanocinnamate, a lipoxygenase inhibitor, and 4 microM 17-octadecynoic acid, an inhibitor of cytochrome P-450 monooxygenases, thus indicating that the effect of AA was not mediated by metabolites of AA. The effect did not appear to be the result of changes in membrane fluidity, since 5 microM eicosatetraynoic acid, an AA analogue that is a potent modulator of membrane fluidity, had no effect. Furthermore, the addition of AA to the outside of the patch also had no effect on channel activity. These results indicate that, like the native low-conductance channel, AA is able to directly inhibit ROMK1 channel activity.

scholarly journals K+ channels in the basolateral membrane of rat cortical collecting duct

1995 ◽  
Vol 48 (4) ◽  
pp. 1036-1046 ◽  
Author(s):  
Jochen Hirsch ◽  
Eberhard Schlatter
Keyword(s):  
Collecting Duct ◽  
Basolateral Membrane ◽  
Cortical Collecting Duct ◽  
K Channels
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