Evidence for two mechanisms of amino acid osmolyte release from hippocampal slices

R. Franco, M. E. Torres-Márquez, H. Pasantes-Morales

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

A 30% decrease in osmolarity stimulated 3H-taurine, 3H-GABA and glutamate (followed as 3H-D-aspartate) efflux from rat hippocampal slices. 3H-taurine efflux was activated rapidly but inactivated slowly. It was decreased markedly by 100 μM 5-nitro-(3-phenylpropylamino)benzoic acid (NPPB) and 600 μM niflumic acid and inhibited strongly by tyrphostins AG18, AG879 and AG112 (25-100 μM), suggesting a tyrosine kinase-mediated mechanism. Hyposmolarity activated the mitogen-activated protein kinases (MAPK) extracellular-signal-related kinase-1/2 (ERK1/ERK2) and p38, but blockade of this reaction did not affect 3H-taurine efflux. Hyposmosis also activated phosphatidylinositide 3-kinase (PI3K) and its prevention by wortmannin (100 nM) essentially abolished 3H-taurine efflux. 3H-taurine efflux was insensitive to the protein kinase C (PKC) blocker chelerythrine (2.5 μM) or to cytochalasin E (3 μM). The release of 3H-GABA and 3H-D-aspartate occurred by a different mechanism, characterized by rapid activation and inactivation, insensitivity to NPPB, niflumic acid, tyrphostins or wortmannin. 3H-GABA and 3H-D-aspartate efflux was not due to external [NaCl] decrease, cytosolic Ca2+ increase or depolarization, or to reverse operation of the carrier. This novel mechanism of amino acid release may be mediated by Ca2+-independent exocytosis and modulated by PKC and actin cytoskeleton disruption, as suggested by its inhibition by chelerythrine and potentiation by 100 nM phorbol-12-myristate-13 acetate (PMA) and cytochalasin E. GABA and glutamate osmosensitive efflux may explain the hyposmolarity-elicited increase in amplitude of inhibitory and excitatory post-synaptic potentials in hippocampal slices as well as the hyperexcitability associated with hyponatraemia.

Original languageEnglish (US)
Pages (from-to)791-800
Number of pages10
JournalPflugers Archiv European Journal of Physiology
Volume442
Issue number5
DOIs
StatePublished - 2001

Keywords

  • Hyposmolarity
  • Regulatory volume decrease
  • Swelling
  • Taurine

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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