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Eur J Neurosci. 1999 May;11(5):1515-22.

Long-lasting substance-P-mediated modulation of NMDA-induced rhythmic activity in the lamprey locomotor network involves separate RNA- and protein-synthesis-dependent stages.

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1
Nobel Institute for Neurophysiology, Department of Neurosciences, Karolinska Institute, Stockholm, Sweden. david.parker@neuro.ki.se

Abstract

Bath application of the tachykinin neuropeptide substance P (1 microm) for 10 min causes long-lasting (> 24 h) modulation of the frequency and regularity of NMDA-evoked locomotor bursts in the lamprey. The change in burst frequency has an induction phase (< 2 h), which depends on the potentiation of NMDA responses and an increase in intracellular calcium levels, and a maintenance phase (> 2 h), that is blocked by translational protein synthesis inhibitors. Here, the maintenance phase has been examined further. Unlike translation inhibitors, the transcription inhibitors actinomycin D and 5,6-dichlorobenzimidazole riboside (DRB) failed to reverse the change in burst frequency 2-3 h after substance P application, suggesting that the protein synthesized at this time does not require de novo RNA synthesis. Transcription inhibitors, however, reversed the change in burst frequency 15-24 h after substance P application, as did brefeldin A, which disrupts the Golgi complex and thus interferes with the post-translational transport of proteins. The change in burst regularity was unaffected by transcription or translation inhibitors, but was partially reversed by protein kinase A inhibitors applied 2.5-8 h after substance P. The glycoprotein synthesis inhibitor 2-deoxygalactose did not affect the changes in burst frequency or burst regularity. These results suggest that there are two phases to the maintenance of the change in burst frequency: an intermediate protein-, but not RNA-, synthesis-dependent phase, and a final RNA-synthesis-dependent phase. The change in burst regularity is protein-synthesis-independent, but may depend on activation of protein kinase A for at least 8 h after substance P application.

[Indexed for MEDLINE]

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