Intracerebroventricular injection of the N-terminal substance P fragment SP(1-7) regulates the expression of the N-methyl-D-aspartate receptor NR1, NR2A and NR2B subunit mRNAs in the rat brain.
Studies have implicated substance P (SP) in the regulation of affective behaviour, memory function, pain influx, stress and opioid reward. All these dimensions are known to involve glutamate transmission mediated through the N-methyl-D-aspartate (NMDA) receptor. The SP N-terminal fragment SP(1-7) is shown to share some but oppose other effects of the parent compound. We have examined the effect of intracerebroventricular injections of SP(1-7) on the expression of the NMDA receptor subunits NR1, NR2A and NR2B mRNAs in the spinal cord and in discrete areas of the male rat brain. The results indicated that the heptapeptide induced a dose-dependent upregulation of the NR2A transcript in hippocampus, periaqueductal grey and ventral tegmental area, already within a few hours. The level of the NR2B mRNA was increased in hippocampus and nucleus accumbens. The expression of the transcript of the NR1 was enhanced in hippocampus and nucleus accumbens but attenuated in spinal cord. The observed effects of the SP(1-7) fragment are in agreement with what could be expected from the known effects of the heptapeptide on various behaviours involving glutamate transmission.
Zhou
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Department of Pharmaceutical Biosciences, Division of Biological Research on Drug Dependence, Uppsala University, PO Box 591, S-751 24, Uppsala, Sweden.
Le Grevés
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P
Ragnar
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Nyberg
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F
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics; D013373:Substance P / Q000008:administration & dosage* / Q000494:pharmacology*
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D010446:Peptide Fragments; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D013373:Substance P; C036877:substance P (1-7)