RESUMEN
1. Our method of real-time monitoring of dopamine release from rat striatal slices revealed that endothelin (ET)-3-induced dopamine release was inhibited by NG-methyl-L-arginine (L-NMMA; 1 mM), an inhibitor of nitric oxide (NO) synthase, while NG-methyl-D-arginine (D-NMMA; 1 mM), an inactive isomer of L-NMMA, had no effect. 2. The inhibition of L-NMMA (0.1 mM) became apparent when tissues were pretreated with tetrodotoxin (1 microM) for 30 min and subsequently exposed to ET-3 (4 microM). 3. L-NMMA (0.1 and 1 mM) dose dependently protected against ET-3-triggered hypoxic/hypoglycemic impairment of striatal responses to high K+. 4. Thus, NO may work as a promoter in mediation of the stimulatory and neurotoxic action of ET-3 on the striatal dopaminergic system, presumably by interacting with interneurons in the striatum.
Asunto(s)
Cuerpo Estriado/citología , Endotelina-3/metabolismo , Interneuronas/metabolismo , Neurotoxinas/metabolismo , Óxido Nítrico/metabolismo , Animales , Hipoxia de la Célula/fisiología , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Dopamina/fisiología , Endotelina-3/farmacología , Inhibidores Enzimáticos/farmacología , Hipoglucemia/fisiopatología , Interneuronas/química , Interneuronas/efectos de los fármacos , Masculino , Técnicas de Cultivo de Órganos , Oxígeno/farmacología , Potasio/farmacología , Ratas , Ratas Wistar , Tetrodotoxina/farmacología , omega-N-Metilarginina/farmacologíaRESUMEN
Pre-treatment with BAY K 8644, an L-type voltage-gated Ca2+ channels agonist, produced long-term enhancement (LTE) of over 2 h of high K(+)-evoked dopamine release from rat striatal slices. Exposure to BAY K 8644 under Ca(2+)-free conditions did not enhance this release. Thus, a transient activation of L-type voltage-gated Ca2+ channels followed by Ca2+ entry can trigger LTE of the evoked DA release from striatal tissues. This type of LTE in the striatum underlines the importance of presynaptic mechanisms, including L-type voltage-gated Ca2+ channels of 'long-term potentiation' expression.
Asunto(s)
Canales de Calcio/fisiología , Cuerpo Estriado/metabolismo , Dopamina/metabolismo , Potasio/farmacología , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Animales , Agonistas de los Canales de Calcio/farmacología , Electrofisiología , Técnicas In Vitro , Activación del Canal Iónico , Masculino , RatasRESUMEN
The high K(+)-evoked dopamine release from rat striatal slices remained impaired by 50% up to 2 h after pulse exposure of the tissues to endothelin-3, under conditions of hypoglycemia/hypoxia. This striatal dysfunction was significantly improved by D-2-amino-5-phosphonopentanoic acid, a NMDA receptor antagonist, at a much lower concentration than that providing protection against NMDA-evoked dysfunction. In light of these findings, the important role of glutamatergic mechanisms, especially NMDA receptors, in mediating endothelin neurotoxicity warrants further attention.
Asunto(s)
Endotelinas/toxicidad , Neostriado/citología , Neuronas/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/efectos de los fármacos , 2-Amino-5-fosfonovalerato/farmacología , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/toxicidad , Animales , Dopamina/metabolismo , Técnicas In Vitro , Masculino , N-Metilaspartato/toxicidad , Neostriado/efectos de los fármacos , Neostriado/metabolismo , Neuronas/metabolismo , Nifedipino/farmacología , Potasio/farmacología , Cloruro de Potasio/farmacología , Ratas , Ratas WistarRESUMEN
The protective effect of nebracetam on ischemic neuronal damage was histologically examined in the pyramidal cell layer of the hippocampal CA1 subfield 7 days after operation using stroke-prone spontaneously hypertensive rats (SHRSP) subjected to 10-min bilateral carotid occlusion. Nebracetam (50 and 100 mg/kg), given orally 10 min after reperfusion, dose-dependently protected against ischemic delayed neuronal damage in the SHRSP with occlusion; however, the blood pressure remained unchanged following nebracetam administration. These findings further support the notion that nebracetam protects against ischemic delayed neuronal cell death in the hippocampus.
Asunto(s)
Parasimpaticomiméticos/farmacología , Pirrolidinonas/farmacología , Animales , Isquemia Encefálica , Recuento de Células/efectos de los fármacos , Hipocampo , Hipertensión , Masculino , Fármacos Neuroprotectores , Células Piramidales/citología , Ratas , Ratas Endogámicas SHRRESUMEN
We examined the role of endothelin (ET) receptor subtypes in mediating the transient and sustained release of dopamine (DA) evoked by ETs and ET-1-induced dopaminergic dysfunction in rat striatal slices. Both phases of the release of DA evoked by ET-1 and ET-3 were inhibited by RES-701-1 (ETB antagonist) but not BQ-123 (ETA antagonist). The high K(+)-evoked DA release from slices remained impaired following a brief exposure to ET-1, under conditions of hypoxia/hypoglycaemia. RES-701-1 but not BQ-123 led to a recovery from ET-1-induced striatal dysfunction. Therefore, ETB receptors are involved in the stimulatory and neurotoxic actions of ETs on the striatal dopaminergic system.