Differentiation of σ ligand‐activated receptor subtypes that modulate NMDA‐evoked [³H]‐noradrenaline release in rat hippocampal slices

Abstract

1It is now widely accepted that there are two classes of sigma (a) binding sites, denoted and°2, and recently 3 subtype has been proposed. Selective c, and c2 receptor agonists are known to modulate the neuronal response to N-methyl-D-aspartate (NMDA) Conversely, N,N-dipropyl-2-[4-methoxy-3-(2-phenylethoxy)phenyl]-ethylamine monohydrochloride (NE-100) blocked the effects of (+)-pentazocine as well as those of BD-737, but not those of DTG. 5 The present results provide in vitro functional evidence for a a receptor type preferentially sensitive to BD-737, reduced haloperidol, BD-1008 and also to NE-100, that differs from the already identified ci, ci2 and ci3 sites.

The Role of Sigma Receptors in Depression

“…1) and these molecules act as antagonists by preventing the potentiation induced by low doses of other sigma agonists (29). A similar bell-shaped doseresponse curve has also been described with sigma ligands in other models such as in release experiments (30) and in behavioral models (28,34). The exact reason for such bell-shaped dose-response curves obtained in so many models have not been well established.…”

σ1 Receptor Modulation of G-Protein-Coupled Receptor Signaling: Potentiation of Opioid Transduction Independent from Receptor Binding

“…Indeed, there is debate about whether they fulfill all of the criteria of a classic receptor. 1 Receptors were initially classified within the opioid receptor family based on their affinity for the (ϩ)isomers of several benzomorphans, and their actions were believed to be associated with opioid action, but they have now been linked to wide range of diverse biological phenomena extending beyond G-protein-coupled receptors, including voltage-gated potassium channels (Lupardus et al, 2000) and NMDA receptors (Monnet et al, 1996;Bermack and Debonnel, 2005). The potential complexity of receptors has been further increased with suggestions of as-yet-unidentified receptor subtypes (Ueda et al, 2001;Bermack and Debonnel, 2005).…”

“…Furthermore, 1 receptors have a far wider range of actions beyond G-protein-coupled receptors. Others have shown an important role of 1 receptors in both Kv1.4 potassium channels (Lupardus et al, 2000;Aydar et al, 2002) and NMDA receptors (Monnet et al, 1996;Martina et al, 2007). These interactions with monovalent and divalent ion channels and with G-protein-coupled receptors raise more questions on the mechanisms of action and overall role of 1 receptors.…”

“…Receptors physically associate with diverse cellular systems, including lipid microdomains (Hayashi and Su, 2003), Kv1.4 potassium channels (Aydar et al, 2002) and NMDA receptors (Monnet et al, 1996;Martina et al, 2007), and it has been suggested recently that they have endoplasmic reticulum chaperone functions (Hayashi and Su, 2007). However, many fundamental questions regarding the functional significance of binding sites remain unanswered.…”

The cholinergic system, sigma-1 receptors and cognition

“…At low doses the NMDA response is potentiated but at higher dose the potentiation is reversed [5,8,111,112]. For example, the sigma-1 receptor agonist SR 31742A increases NMDA-induced inward currents of pyramidal cells in slices of rat medial prefrontal cortex at doses ranging from 10 nM to 100 nM (EC 50 23 nM), but at doses greater than 100 nM an inhibition is observed [66].…”