Molecular and Cellular Endocrinology 162 (2000) 203 – 210 Volume-sensitive amino acid efflux from a pancreatic -cell line A.C.G. Grant, J. Thomson, V.A. Zammit, D.B. Shennan * Hannah Research Institute, Ayr, KA65HL, Scotland, UK Received 10 September 1999; accepted 15 December 1999 Abstract Cell swelling, induced by a hyposmotic shock, increased the fractional release of taurine from INS-1 cells. Volume-sensitive taurine release was (a) dependent upon the extent of cell swelling; (b) fully reversible; and (c) temperature dependent. Volume-sensitive taurine efflux was independent from the trans -membrane Na + -gradient. DIDS markedly inhibited volume-acti- vated taurine efflux but not basal taurine release suggesting that the volume-sensitive pathway is quiescent under isosmotic conditions. Volume-activated taurine release inactivated in the continued presence of a hyposmotic shock. Cell-swelling also increased the fractional release of D-aspartate from INS-1 cells. Volume-activated D-aspartate efflux was inhibited by DIDS, albeit to a lesser extent than volume-sensitive taurine release. It is predicted that volume-sensitive amino acid efflux acts in parallel with other volume-activated transport mechanisms to regulate the volume of insulin-secreting cells. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Animo acid efflux; Pancreatic  cell line; Cell swelling; Hyposmotic shock www.elsevier.com/locate/mce 1. Introduction Most cells are capable of regulating their volume following swelling induced by anisosmotic conditions, substrate accumulation and/or oxidative metabolism (for reviews see Hoffmann and Simonsen, 1989; Haussinger, 1996). Increasing the cellular hydration state activates a variety of membrane transport systems which leads to a net loss of intracellular osmolytes and water and thus allows cells to return towards a normal volume: this process is termed a regulatory volume decrease (RVD). For example, cell swelling is known to activate K + and Cl - transport via systems such as (K + –Cl - ) cotransport and separate K + and Cl - con- ductances (Hoffmann and Simonsen, 1989). In addi- tion, an increase in cell volume stimulates the release of amino acids such as taurine via a system that has the characteristics of a channel rather than a carrier (Kinne, 1993; Strange et al., 1996; Kirk, 1997). It has recently been reported that an increase in cell volume activates an anion conductance in pancreatic islet and insulinoma (RINm5F, HIT-T15) cells (Kinard and Satin, 1995; Best et al., 1996, 1997; Drews et al., 1998). The available evidence suggests that the volume- activated anion conductance helps to facilitate a RVD in insulin-secreting cells (Best et al., 1996). Moreover, the volume-activated anion conductance may play a major role in insulin release as a consequence of depo- larising the membrane potential (Best et al., 1996).This is consistent with earlier findings that a hyposmotic challenge increases insulin release from pancreatic - cells in a fashion dependent upon the extent of cell swelling (Blackard et al., 1975; Marcstrom et al., 1990; Miley et al., 1997). Given the relationship between cell volume and in- sulin secretion it is important that the mechanisms activated by cell-swelling in insulin-secreting cells are thoroughly characterised. In view of this we have inves- tigated the effect of cell swelling on the efflux of amino acids from insulin secreting cells since volume-activated amino acid transport may be involved in cell volume regulation (Hoffmann and Simonsen, 1989). We have studied the effect of cell swelling on the transport of amino acids from INS-1 cells. These cells are consid- ered to be a suitable model for studying various aspects of -cell function (e.g. see Asfari et al., 1992; Rutter et * Corresponding author. Tel.: +44-01292-674066; fax: +44- 01292-674003. E-mail address: shennand@hri.sari.ac.uk (D.B. Shennan) 0303-7207/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII:S0303-7207(99)00260-9