Ca(2+)-mobilizing hormones potentiate hypotonicity-induced activation of ionic conductances in Intestine 407 cells

Abstract

Human Intestine 407 cells respond to hyposmotic stimulation by activating the conductive efflux of both Cl- and K+ (regulatory volume decrease) through pathways involving protein tyrosine phosphorylation (Tilly, B. C., N. van den Berghe, L. G. J. Tertoolen, M. J. Edixhoven, and H. R. de Jonge. J. Biol. Chem. 268: 19919-19922, 1993). Stimulation of the cells with hormones linked to the phospholipase C signaling cascade (e.g., bradykinin, histamine, or thrombin) or with the phosphotyrosine phosphatase inhibitor vanadate, potentiated the osmosensitive anion efflux by two- to threefold but did not affect anion efflux under isotonic conditions. No substantial increase in intracellular Ca2+ concentration ([Ca2+]i) was observed on mild hypotonicity-induced cell swelling. In addition, loading the cells with the intracellular Ca2+ chelator 1,2-bis(2-amino-phenoxy)ethane- N,N,N',N',-tetraacetic acid acetoxymethyl ester (BAPTA-AM) caused a partial reduction of the osmoshock-induced 125I- efflux but did not affect its potentiation by vanadate. In contrast, bradykinin transiently elevated [Ca2+]i, and its potentiation of the osmosensitive anion efflux was completely inhibited after BAPTA-AM loading. Both the Ca(2+)-mobilizing hormones as well as osmotic cell swelling rapidly triggered the phosphorylation of several proteins on tyrosine residues. However, the effects of the hormones, but not the effect of hypotonicity, on protein tyrosine phosphorylation was largely abolished in BAPTA-loaded cells. Taken together the results indicate a novel role for Ca(2+)-mobilizing hormones, although elevation of [Ca2+]i, in potentiating volume-sensitive ionic efflux even in cell types lacking the expression of Ca(2+)-activated Cl- channels in their plasma membrane.

Activation of P2Y receptors causes strong and persistent shrinkage of C11-MDCK renal epithelial cells

“…It has become increasingly clear that agonists of these receptors, and ATP in particular, may accelerate cell-volume recovery under anisosmotic conditions and potently modulate volume-sensitive channels as well as transporters in cells, even in the absence of cell-volume changes (15,28,30,54). It has also been established that signaling linked to G protein-coupled receptors may impact cell volume, as, for example, in mouse Means Ϯ SE values (in nmol/mg of protein) from experiments performed in triplicate are shown.…”

Hypotonicity activates transcription through ERK-dependent and -independent pathways in renal cells

“…The signaling events leading to activation of inorganic ion and organic solute efflux pathways remain obscure. Prior investigations have broadly implicated phosphorylation events (17,37,41,55,57) and a mitogen-activated protein kinase (MAPK) (57).MAPKs transduce cellular signals (such as those perceived at the cell membrane in response to stressors and peptide mitogens) into nuclear transactivation events. Members of the extracellular signal response kinase (ERK) family of MAPKs are phosphorylated and activated by MAPK or ERK kinases (MEKs); on activation, ERKs phosphorylate and activate the transcription factor Elk-1, among other substrates (24).…”

“…The signaling events leading to activation of inorganic ion and organic solute efflux pathways remain obscure. Prior investigations have broadly implicated phosphorylation events (17,37,41,55,57) and a mitogen-activated protein kinase (MAPK) (57).…”

P2X4 Activation Modulates Volume-sensitive Outwardly Rectifying Chloride Channels in Rat Hepatoma Cells

“…For example, in an intestinal cell line (44) and in a neuroblastoma cell line (45), activation of the thrombin receptor induces at least a 2-fold increase in I Ϫ efflux. Furthermore, fibroblasts (46) show not only an increase in VSOR Cl Ϫ current but also a decrease in the half-time for current onset after thrombin receptor activation.…”