11,12-Epoxyeicosatrienoic acid induces vasodilator response in the rat perfused mesenteric vasculature

Bihzad, S. M.; Yousif, Mariam H. M.

doi:10.1111/aap.12052

Cited by 3 publications

(4 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The endogenous TRPV4 agonist 11,12-epoxyeicosatrienoic acid also inhibits b-arrestin recruitment to AT1R (Fig. S2A) (20). Interestingly, 10 nM GSK101 alone is sufficient to significantly decrease b-arrestin recruitment and luciferase production compared with baseline, which could indicate a reduction in ligand-independent phosphorylation (Fig.…”

Section: Trpv4 Inhibits At1r Phosphorylationmentioning

confidence: 87%

The nonselective cation channel TRPV4 inhibits angiotensin II receptors

Zaccor

Sumner

Snyder

2020

Journal of Biological Chemistry

View full text Add to dashboard Cite

G-protein–coupled receptors (GPCRs) are a ubiquitously expressed family of receptor proteins that regulate many physiological functions and other proteins. They act through two dissociable signaling pathways: the exchange of GDP to GTP by linked G-proteins and the recruitment of β-arrestins. GPCRs modulate several members of the transient receptor potential (TRP) channel family of nonselective cation channels. How TRP channels reciprocally regulate GPCR signaling is less well-explored. Here, using an array of biochemical approaches, including immunoprecipitation and fluorescence, calcium imaging, phosphate radiolabeling, and a β-arrestin–dependent luciferase assay, we characterize a GPCR–TRP channel pair, angiotensin II receptor type 1 (AT1R), and transient receptor potential vanilloid 4 (TRPV4), in primary murine choroid plexus epithelial cells and immortalized cell lines. We found that AT1R and TRPV4 are binding partners and that activation of AT1R by angiotensin II (ANGII) elicits β-arrestin–dependent inhibition and internalization of TRPV4. Activating TRPV4 with endogenous and synthetic agonists inhibited angiotensin II–mediated G-protein–associated second messenger accumulation, AT1R receptor phosphorylation, and β-arrestin recruitment. We also noted that TRPV4 inhibits AT1R phosphorylation by activating the calcium-activated phosphatase calcineurin in a Ca2+/calmodulin–dependent manner, preventing β-arrestin recruitment and receptor internalization. These findings suggest that when TRP channels and GPCRs are co-expressed in the same tissues, many of these channels can inhibit GPCR desensitization.

show abstract

Section: Trpv4 Inhibits At1r Phosphorylationmentioning

confidence: 87%

The nonselective cation channel TRPV4 inhibits angiotensin II receptors

Zaccor

Sumner

Snyder

2020

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…In normal mice, 11,12‐EET (11,12‐epoxyeicosatrienoic acid) induces the hyperpolarization of vascular smooth muscle cell membranes and the vasodilation of mesenteric arteries, but after the activity of Trpv4 in the endothelium is disrupted, hyperpolarization and vasodilation induced by 11,12‐EET are decreased by half 19 . Likewise, the 11,12‐EET‐induced vasodilation response is also markedly reduced in the tissues of diabetic animals or in tissues incubated with the TRPV4 inhibitor ruthenium red 40 .…”

Section: Trpv4 and Diabetes‐related Cardiovascular Diseasesmentioning

confidence: 99%

“…Furthermore, inhibiting or attenuating TRPV4 activity might reduce high‐fat diet (HFD)‐induced obesity and inflammation 10 . Table 1 summarizes recent findings on the involvement of TRPV4 in the pathogenesis of type 2 diabetes and diabetes‐related diseases 9‐49 . Even though TRPV4 might play a significant role in the development of diabetes and related conditions, the underlying mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Transient receptor potential vanilloid 4 channels as therapeutic targets in diabetes and diabetes‐related complications

Ding

et al. 2020

J of Diabetes Invest

View full text Add to dashboard Cite

With an estimated 425 million diabetes patients worldwide in 2019, type 2 diabetes has reached a pandemic proportion and represents a major unmet medical need. A key determinant of the development and progression of type 2 diabetes is pancreatic-cell dysfunction, including the loss of cell mass, the impairment of insulin biosynthesis and inadequate exocytosis. Recent studies have shown that transient receptor potential vanilloid 4 (TRPV4), a Ca 2+-permeable non-selective cation channel, is involved in-cell replication, insulin production and secretion. TRPV4 agonists have insulinotropic activity in pancreatic-cell lines, but the prolonged activation of TRPV4 leads to-cell dysfunction and death. In addition, TRPV4 is involved in a wide variety of pathophysiological activities, and has been reported to play an important role in diabetes-related complications, such as obesity, cardiovascular diseases, diabetic retinopathy, nephropathy and neuropathy. In a rodent type 2 diabetes model, Trpv4 agonists promote vasodilation and improve cardiovascular function, whereas Trpv4 antagonists reduce high-fat diet-induced obesity, insulin resistance, diabetic nephropathy, retinopathy and neuropathy. These findings raise interest in using TRPV4 as a therapeutic target for type 2 diabetes. In this review, we intend to summarize the latest findings regarding the role of TRPV4 in diabetes as well as diabetesrelated conditions, and to evaluate its potential as a therapeutic target for diabetes and diabetes-related diseases.

show abstract

“…Endothelial cells metabolize arachidonic acid (AA) via CYP450 enzymes (ω-hydroxylase and epoxygenase), via cyclooxygenases and 5-lipooxygenase, and by non-enzymatic degradation of arachidonic acid in the presence of free radicals [ 10 ]. Epoxygenases are members of cytochrome P450 family of enzymes, which in the endothelial cell produce four epoxyeicosatrienoic acid (EET) isomers, of which 14,15-EET and 11,12-EET are the major active vasodilator metabolites [ 10 , 11 , 12 , 13 , 14 , 15 ]. ω-hydroxylase, in smooth muscle cells, promotes the production of 20-hydroxy-eicosatrienoic acid (20-HETE), which is a vasoconstrictor [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1α Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation

Mihaljević

Matić

Stupin

et al. 2020

IJMS

View full text Add to dashboard Cite

Acetylcholine-induced vasorelaxation (AChIR) and responses to reduced pO2 (hypoxia-induced relaxation (HIR), 0% O2) were assessed in vitro in aortic rings of healthy male Sprague-Dawley rats (N = 252) under hyperbaric (HBO2) protocols. The studied groups consisted of the CTRL group (untreated); the A-HBO2 group (single HBO2; 120 min of 100% O2 at 2.0 bars); the 24H-HBO2 group (examined 24 h after single exposure) and the 4D-HBO2 group (four consecutive days of single HBO2). AChIR, sensitivity to ACh and iNOS expression were decreased in the A-HBO2 group. HIR was prostanoid- and epoxyeicosatrienoic acid (EET)-mediated. HIF-1α expression was increased in the 24H-HBO2 and 4D-HBO2 groups. LW6 (HIF-1α inhibitor) decreased HIR in the 24H-HBO2 group. HBO2 affected the expression of COX-1 and COX-2. CYP2c11 expression was elevated in the 24H-HBO2 and 4D-HBO2 groups. Concentrations of arachidonic acid (AA) metabolites 14(15)-DiHET, 11(12)-DiHET and 8(9)-DiHET were increased in A-HBO2 and 24H-HBO2. An increased concentration of 8(9)-EET was observed in the A-HBO2 and 24h-HBO2 groups vs. the CTRL and 4D-HBO2 groups, and an increased concentration of 5(6)-DiHET was observed in the 24H-HBO2 group vs. the 4D-HBO2 group. The 20-HETE concentration was increased in the A-HBO2 group. All were determined by LC-MS/MS of the aorta. The results show that AChIR in all groups is mostly NO-dependent. HIR is undoubtedly mediated by the CYP450 enzymes’ metabolites of AA, whereas HIF-1α contributes to restored HIR. Vasoconstrictor metabolites of CYP450 enzymes contribute to attenuated AChIR and HIR in A-HBO2.

show abstract

11,12-Epoxyeicosatrienoic acid induces vasodilator response in the rat perfused mesenteric vasculature

Cited by 3 publications

References 42 publications

The nonselective cation channel TRPV4 inhibits angiotensin II receptors

The nonselective cation channel TRPV4 inhibits angiotensin II receptors

Transient receptor potential vanilloid 4 channels as therapeutic targets in diabetes and diabetes‐related complications

Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1α Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation

Contact Info

Product

Resources

About