RESUMO
NMDA receptors bidirectionally modulate extracellular signal-regulated kinase (ERK) through the coupling of synaptic NMDA receptors to an ERK activation pathway that is opposed by a dominant ERK shutoff pathway thought to be coupled to extrasynaptic NMDA receptors. In the present study, synaptic NMDA receptor activation of ERK in rat cortical cultures was partially inhibited by the highly selective NR2B antagonist Ro25-6981 (Ro) and the less selective NR2A antagonist NVP-AAM077 (NVP). When Ro and NVP were added together, inhibition appeared additive and equal to that observed with the NMDA open-channel blocker MK-801. Consistent with a selective coupling of extrasynaptic NMDA receptors to the dominant ERK shutoff pathway, pre-block of synaptic NMDA receptors with MK-801 did not alter the inhibitory effect of bath-applied NMDA on ERK activity. Lastly, in contrast to a complete block of synaptic NMDA receptor activation of ERK by extrasynaptic NMDA receptors, activation of extrasynaptic NMDA receptors had no effect upon ERK activation by brain-derived neurotrophic factor. These results suggest that the synaptic NMDA receptor ERK activation pathway is coupled to both NR2A and NR2B containing receptors, and that the extrasynaptic NMDA receptor ERK inhibitory pathway is not a non-selective global ERK shutoff.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/fisiologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Receptores de N-Metil-D-Aspartato/fisiologia , Transdução de Sinais/efeitos dos fármacos , Animais , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Córtex Cerebral/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/biossíntese , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Maleato de Dizocilpina , Ativação Enzimática/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , N-Metilaspartato , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Técnicas de Patch-Clamp , Fenóis/farmacologia , Piperidinas/farmacologia , Quinoxalinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
The presence of 3,4-benzopyrene is reported in samples of water and sediments from three briny ponds free from pollution of exogenous origin belonging to three different atolls of Polynesia. The synthesis of this hydrocarbon seems to be dependent on the presence of abundant phytoplancton and of bacterial flora.