Epidermal growth factor as a diuretic in sheep.

Gow, C. B.; Phillips, Paddy A.

doi:10.1113/jphysiol.1994.sp020168

Cited by 17 publications

(10 citation statements)

References 20 publications

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“…16 The idea that EGF may play a role in water balance was previously suggested by Gow and Phillips, 17 because they showed that EGF infusion in sheep resulted in brisk diuresis and natriuresis. Therefore, we used erlotinib, a Food and Drug Administration (FDA) -approved EGFR inhibitor, 18,19 to study the underlying pathways affected by EGF inhibition in water balance.…”

mentioning

confidence: 99%

EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2–Mediated Renal Water Reabsorption

Cheung

Nomura

Nair

et al. 2016

JASN

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Nephrogenic diabetes insipidus (NDI) is caused by impairment of vasopressin (VP) receptor type 2 signaling. Because potential therapies for NDI that target the canonical VP/cAMP/protein kinase A pathway have so far proven ineffective, alternative strategies for modulating aquaporin 2 (AQP2) trafficking have been sought. Successful identification of compounds by our high-throughput chemical screening assay prompted us to determine whether EGF receptor (EGFR) inhibitors stimulate AQP2 trafficking and reduce urine output. Erlotinib, a selective EGFR inhibitor, enhanced AQP2 apical membrane expression in collecting duct principal cells and reduced urine volume by 45% after 5 days of treatment in mice with lithiuminduced NDI. Similar to VP, erlotinib increased exocytosis and decreased endocytosis in LLC-PK1 cells, resulting in a significant increase in AQP2 membrane accumulation. Erlotinib increased phosphorylation of AQP2 at Ser-256 and Ser-269 and decreased phosphorylation at Ser-261 in a dose-dependent manner. However, unlike VP, the effect of erlotinib was independent of cAMP, cGMP, and protein kinase A. Conversely, EGF reduced VP-induced AQP2 Ser-256 phosphorylation, suggesting crosstalk between VP and EGF in AQP2 trafficking and a role of EGF in water homeostasis. These results reveal a novel pathway that contributes to the regulation of AQP2-mediated water reabsorption and suggest new potential therapeutic strategies for NDI treatment.

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confidence: 99%

EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2–Mediated Renal Water Reabsorption

Cheung

Nomura

Nair

et al. 2016

JASN

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“…for 8 days (days [13][14][15][16][17][18][19][20]. On days 5-16, blood samples (30mL) were collected at 09.00h.…”

Section: Methodsmentioning

confidence: 99%

“…Where a significant interaction was obtained, simple main effects were determined. The a priori data of interest were those comparing EGF treatment versus control treatment, EGF + indomethacin treatment versus indomethacin treatment and EGF + indomethacin treatment versus EGF treatment during the period of treatment (days 9-12) and the subsequent period after this (days [13][14][15][16][17][18][19][20]. Statistical differences between individual means were calculated using the Newman-Keul's post hoc comparisons test.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…Also, the highest value of urine volume was an increase of 226+21 and 125&32% above values recorded during the -Daily (a) urine volume and (b) water intake of ewes before, during and after treatment with epidermal growth factor (EGF) and/or indomethacin. Ewes received a continuous infusion of saline (150 mL/day) for 8 days (days 1-8) and then either vehicle (solid line; n = 5), 15 pg EGFh (0, W; n = 5), 2 mgkg per day indomethacin (A, A; n = 5 ) or 15 pgih EGF with 2 mgkg per day indomethacin (0, 0; n = 5) in 150 &day saline for 4 days (days 9-12) followed by saline (150&day) for 8 days (days[13][14][15][16][17][18][19][20].Open symbols, periods of saline infusion; filled symbols, the period of EGF and/or indomethacin infusion. Data are the mean ?…”

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confidence: 99%

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Effects of Indomethacin on Epidermal Growth Factor‐induced Renal Responses in Sheep

Gow

Grant

Phillips

1997

Clin Exp Pharma Physio

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1. The effects of indomethacin (an inhibitor of prostaglandin synthesis) on the renal responses to epidermal growth factor (EGF) were investigated in conscious sheep. 2. Ewes (n = 5 per group) received an i.v. saline infusion (150 mL/day) for days 1-8, followed by either vehicle control, 15 micrograms/h EGF, 2 mg/kg per day indomethacin or 15 micrograms/h EGF with 2 mg/kg per day indomethacin in 150 mL/day saline, i.v., over days 9-12. All ewes subsequently received an i.v. saline infusion (150 mL/day) over days 13-20. 3. Polydipsia, diuresis, transient natriuresis and reduced urine osmolality occurred during EGF treatment alone. There was no effect of EGF on fluid balance, plasma electrolyte or hormone concentrations, plasma osmolality or haematocrit or on the urinary excretion of potassium. 4. Simultaneous infusion of indomethacin with EGF attenuated (P < 0.05) the stimulatory effects of EGF infusion alone on urine volume, water intake, natriuresis and urine osmolality. 5. We conclude that prostaglandins may be involved in the diuretic/natriuretic effects of EGF, but may not be the sole mechanism involved.

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“…The pharmacological interest in the peptide for use in humans has mainly focused on its role in accelerating wound healing and tissue repair by local and systemic applications [7]. Recently, it was also demonstrated that administration of EGF had an isolated diuretic effect in rats [8], and it has been suggested that EGF antagonizes vasopressin action inducing diuresis in sheep [9, 10]. However, the cellular mechanism for this is not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Long-Term EGF Treatment Partially Prevents Reduction of Renal Blood Flow in Response to Neonatally Induced Partial Unilateral Ureteral Obstruction

Wen

Wang²,

Chen³

et al. 2009

Nephron Exp Nephrol

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Background/Aims: To investigate the effects of long-term epidermal growth factor (EGF) treatment on kidney growth, renal blood flow (RBF), AQP2 expression and urine output in newborn rats with partial unilateral ureteral obstruction (PUUO). Methods: PUUO (n = 29) and sham-operated control (CON) (n = 26) was created in 2-day-old rats. Fifteen PUUO and 14 CON rats were treated with EGF beginning from the second day after operation to 8 weeks of age. Total kidney volume (TKV) and RBF were measured by MRI at weeks 4 and 8, respectively. Urine volume and osmolality, plasma osmolality, and free water clearance were measured. Renal AQP2 expression was determined using semiquantitative immunoblotting. Results: PUUO induced a severe hydronephrosis and RBF reduction in the obstructed kidney which was attenuated in EGF-treated rats. Body weight, urine output and free water clearance increased, osmolality and the osmolar clearance decreased significantly in EGF-treated rats, despite unchanged AQP2 levels. Conclusions: Long-term EGF treatment attenuated the obstruction- induced RBF reduction. Body weight, urine output increased, and urine osmolality decreased in both control and PUUO rats treated with EGF. Solute-free water clearance increased in PUUO rats which seem to be independent of AQP2 expression.

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Epidermal growth factor as a diuretic in sheep.

Cited by 17 publications

References 20 publications

EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2–Mediated Renal Water Reabsorption

EGF Receptor Inhibition by Erlotinib Increases Aquaporin 2–Mediated Renal Water Reabsorption

Effects of Indomethacin on Epidermal Growth Factor‐induced Renal Responses in Sheep

Long-Term EGF Treatment Partially Prevents Reduction of Renal Blood Flow in Response to Neonatally Induced Partial Unilateral Ureteral Obstruction

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