Hyperosmotic activation of the Na(+)‐H+ exchanger in a rat bone cell line: temperature dependence and activation pathways.

Abstract

SUMMARY1. The hyperosmotic activation of the Na+-H+ exchanger was studied in an osteoblast-like rat cell line (RCJ 1.20 to the stimulatory effects of these agents, suggesting an independent hyperosmotic activation pathway. 5. The hyperosmotic activation of the Na+-H+ exchanger was independent of cAMP, cGMP, cytosolic Ca2+ and protein kinase C. Thus, none of the classical transduction mechanisms seem to be involved directly in the hyperosmotic activation of the antiporter.6. The pHi response induced by the hyperosmotic stress was abolished by two t To whom correspondence should be addressed. PHY 456 A. DASCALU, Z. NEVO AND R. KORENSTEIN calmodulin inhibitors, W-7 and chlorpromazine (50 % inhibition, Ki at 28 and 20 pM, respectively), 20 /tM cytochalasin B, but not by 10 /LM colchicine. The results suggest the involvement of actin and calmodulin-like structural elements of the cytoskeleton in the transduction process leading to the activation of the Na+-H+ exchanger.

Ionic mechanisms contributing to the vasorelaxant properties of iodinated contrast media: a comparison of iohexol and iodixanol in the rabbit isolated aorta

“…This spatial clustering may facilitate interactions between the Na -K+ pump and Na + -Ca2 + exchanger. Several studies have demonstrated that high concentrations of mannitol and sucrose also activate Na+ -H+ exchange (Whalley et al, 1991;Dascalu et al, 1992;Toda et al, 1992;Soleimani et al, 1995). In rat aorta EIPA blocks the Na+ -H+ antiporter with an ICs0 of 19 nM and also inhibits Na+ -Ca2+ exchange with an IC50 of 261 gM (Bingham-Smith et al, 1991).…”

Hyperosmotic modulation of the cytosolic calcium concentration in a rat osteoblast‐like cell line.

“…Fura-2 AM was purchased from Molecular Probes, Inc., Eugene, OR, USA. In a previous study of hyperosmotic effects (Dascalu, Nevo & Korenstein, 1992) (100 EM, A) and Gd3+ (100 EM, B)…”

“…Hyposmotic stimuli were found to elevate [Ca2+], in osteosarcomaderived bone cells (Yamaguchi, Green, Kleeman & Muallem, 1989). A hyperosmotic stimulus alters the intracellular pH (pHJ) in rat osteoblasts (Dascalu, Nevo & Korenstein, 1992) and causes an increase in [Ca2+]i in lymphocytes (Grinstein, Dupre & Rothstein, 1982). In addition, the mechanisms responsible for pHi regulation in an osteosarcoma cell line were modulated by [Ca2+]i (Green & Kleeman, 1992), reflecting a complex interaction between pH, and [Ca2+], (Dickens, Gillespie, Greenwell & Hutchinson, 1990 …”

Structure/function studies of mammalian Na‐H exchangers‐‐an update.

“…Current postulated mechanisms for the hyperosmolar effect are by inducing change in the physicochemical property of the cell membrane, concentration of intracellular solutes or cytosolic macromolecules or G proteins (Garner & Burg, 1994). Involvement of protein kinase C (Grinstein et al 1986), Ca2+/CaM-dependent kinase (Dascalu et al 1992;Chinet, 1993), and phosphorylation-independent mechanisms (Grinstein et al 1992) have been suggested. However, we have found that protein kinase C, tyrosine kinase, elevation of Ca2+, cyclic AMP, and cytoskeletal elements including inhibition of microtubules and actin did not affect the hyperosmolarity-induced NHE3 inhibition .…”