RT info:eu-repo/semantics/article
T1 Osmosensitive response of glutamate in the substantia nigra.
A1 Morales Pérez, Ingrid
A1 Fuentes, Ángel
A1 González Hernández, Tomás
A1 Rodríguez, Manuel
A2 Ciencias de la Comunicación y Trabajo Social
A2 Grupo de Neurobiología y Neurología Experimental
K1 Glutamate
K1 ATP
K1 Substantia nigra
K1 Osmoregulation
K1 Swelling
K1 Parkinson's disease
AB Previous studies have suggested the increase of extracellular glutamate (GLU) in the substantia nigra (SN) as a cause of dopamine-cell degeneration (excitotoxicity) in Parkinson's disease (PD). However, the mechanisms involved in this increase remain unknown. The present work studied osmoregulation as a cause of GLU release in the SN. Microdialysis was used to change extracellular osmolarity, to administer drugs and to quantify the extracellular non-synaptic GLU (EnS-GLU). Two osmolarity modifications were performed, a moderate decrease (5%) resembling physiological modifications and a substantial decrease (≥20% decrease) similar to that observed under pathological conditions. Hypo-osmolarity induced a doseresponse (285–80 mOsm) increase of EnS-GLU which was detected after small osmolarity modifications (15 mOsm) and which was very marked (N1000%) after more intense osmolarity changes. This response disappeared after pre-treating rats with a P2 purinergic-receptor antagonist (pyridoxalphosphate-6azophenyl-2′,4′-disulphonic acid; 1 mM) suggesting ATP involvement in the osmosensitive EnS-GLU response. The EnS-GLU increase observed after administration of ATP (0.1–100 μM) and 2-methylthioadenosine triphosphate tetrasodium (P2-receptor agonist; 100 μM) and the lack of effects of adenosine administration (1 mM) suggest that the ATP action on P2 receptors is an amplificatory mechanism in the osmosensitive EnS-GLU response. The marked action of osmolarity on extracellular Glu suggests osmolarity regulation as a possible source for excitotoxicity in the SN.
YR 2009
FD 2009
LK http://riull.ull.es/xmlui/handle/915/38561
UL http://riull.ull.es/xmlui/handle/915/38561
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 18-oct-2024