Epidermal growth factor inhibits the hydroosmotic effect of vasopressin in the isolated perfused rabbit cortical collecting tubule.

Abstract

Epidermal growth factor (EGF) is a 53-amino acid polypetide which is a potent mitogen for cultured cells. The kidney has recently been shown to be a major site of synthesis for the EGF precursor. EGF infusions in sheep result in a diuresis and natriuresis despite a fall in GFR, suggesting a direct tubular effect. Using in vitro microperfusion of rabbit cortical collecting tubules (CC1s) at 370C, we examined the effect of EGF on the transepithelial voltage (VJ) and arginine vasopressin (AVP)-stimulated hydraulic conductivity (Lp). Pretreatment with peritubular EGF at concentrations from lo-8 to 10-12 M resulted in a 50% inhibition of both AVP-and 8-chlorophenythio-cyclic AMP-stimulated peak Lp. This effect was reversed by the protein kinase C inhibitor, staurosporine, but unaffected by indomethacin. CCTs with an initially negative V,, depolarized after exposure to bath EGF. 10-8 M EGF applied from the lumen had no effect on either Lp or Vt. Specific binding of 20 nM 125I-EGF to microdissected CCITs was also demonstrated. These results suggest that EGF can modulate both salt and water transport in the CCI via a receptor linked to protein kinase C activation.

Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor.

“…In the mouse submaxillary gland, prepro-EGF is processed intracellularly to the 53-amino acid form of the peptide. In contrast, in kidney cells the precursor accumulates and is not processed to mature EGF (17,20 liii.-.~~_ age of the extracellular membrane-bound protein by proteases present in the lumen ofthe nephron or in serum would serve to release EGF and account for the large quantity of the peptide present in urine (7) or in medullary interstitium (17,20 (12,21) and in freshly isolated suspensions (22). Teitelbaum et al (12) reported that EGF stimulates phospholipase C activity in cultured rat inner medullary collecting tubule cells (12).…”

Hyponatremia in cirrhosis: From pathogenesis to treatment†

“…The action of VP to increase water permeability of the collecting duct is modulated by a number of hormones and autacoids, including prostaglandin E 2 (PGE 2 ), endothelin, cholinergic agents, and epidermal growth factor, [37][38][39][40] which act through different pathways. Cellular pathways known to be involved in the inhibition of VP signaling are protein kinase C and the extracellularly regulated protein kinases.…”

Matrix Metalloproteinase 2 (MMP2) and MMP9 Are Produced by Kidney Collecting Duct Principal Cells but Are Differentially Regulated by SV40 Large-T, Arginine Vasopressin, and Epidermal Growth Factor

“…and AVP are physiological ligands of principal cells that exert antagonistic hydroosmotic effects on the collecting duct (30,31). We therefore tested the ability of these factors to regulate the expression of MMP2 and MMP9 in RC.SVtsA58 cells.…”

“…It also raises sodium reabsorption by apical epithelial sodium channels (54). EGF inhibits the hydroosmotic effects of AVP by acting at a post-cAMP level (30). Conversely, AVP inhibits the EGF-stimulated mitogen-activated protein kinase cascade (55), indicating that the signal transduction pathways of AVP and EGF are closely connected in collecting duct cells.…”