Epidermal growth factor selectively enhances NMDA receptor-mediated increase of intracellular Ca2+ concentration in rat hippocampal neurons.
We have previously reported that recombinant human epidermal growth factor (hEGF) facilitates induction of hippocampal long-term potentiation (LTP). In order to clarify the mechanism underlying the LTP-facilitating effect of hEGF, the influence of hEGF on intracellular Ca2+ concentration ([Ca2+]i) of hippocampal neurons was investigated using dissociated cell cultures. Changes in [Ca2+]i were measured by microfluorometrically monitoring the fluorescence intensities from individual neurons loaded with fura-2. Application of hEGF (0.6-20 ng/ml) alone did not affect the basal level of [Ca2+]i in cultured hippocampal neurons, but significantly enhanced the [Ca2+]i increase induced by L-glutamate (3 x 10(-6) M). The N-methyl-D-aspartate (NMDA) (10(-5) and 3 x 10(-5) M)-induced [Ca2+]i increase was also enhanced by hEGF, but the quisqualate (10(-7) and 3 x 10(-7) M)-induced response was not affected by the presence of hEGF. These results suggest that hEGF selectively enhances the NMDA receptor-mediated responses in hippocampal neurons. This action of hEGF may underlie the facilitation of hippocampal LTP.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
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Abe
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D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016257:Fura-2; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D018698:Glutamic Acid; D004815:Epidermal Growth Factor; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D002118:Calcium; D016257:Fura-2