In Vivo Modulation of Sigma Receptor Sites by Calcitonin Gene‐related Peptide in the Mouse and Rat Hippocampal Formation: Radioligand Binding and Electrophysiological Studies
- 1 September 1995
- journal article
- Published by Wiley in European Journal of Neuroscience
- Vol. 7 (9), 1952-1962
- https://doi.org/10.1111/j.1460-9568.1995.tb00718.x
Abstract
Possible interactions between sigma (σ) receptor sites and calcitonin gene‐related peptides (CGRP) were investigated using receptor subtype‐related analogues and fragments in in vivo [3H](+)SKF 10 047/σ binding in the hippocampus, and electrophysiological recording of the N‐methyl‐D‐aspartate (NMDA)‐induced activation of CA3 pyramidal neurons, two well‐established σ assays. In both paradigms, CGRP and the agonist [Cys(ACM)2,7]hCGRPα modulated σ systems. In vivo binding experiments demonstrated that CGRP and [Cys(ACM)2,7]hCGRPα inhibited 25–40% of specific [3H](+)SKF 10 047 labelling in the mouse hippocampal formation while the purported antagonist hCGRP8–37 was inactive. The specificity of this modulation was demonstrated further by the lack of effect of other vasoactive peptides, including the atrial natriuretic peptide, substance P, and its N‐terminal fragment, substance P1–7. In the CA3 subfield of the rat dorsal hippocampus, hCGRPα decreased (up to 61%) the NMDA‐induced activation of the pyramidal neurons. Conversely, the linear analogue [Cys(ACM)2,7]hCGRPα enhanced (by 85%) the NMDA‐induced activation of CA3 pyramidal neurons, while the antagonistic fragment hCGRP8–37 had no effect. Haloperidol, a high‐affinity σ receptor ligand, inhibited by 90% the in vivo [3H](+)SKF 10 047 labelling, and prevented the modulation of the NMDA‐induced activation by hCGRPα and [Cys(ACM)2,7]hCGRPα. It thus appears that CGRP can modulate σ‐related systems in the hippocampal formation.Keywords
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