Sigma (σ) receptors have generated a great deal of interest on the basis of their possible roles in various pathologies, including cytoprotection. Although the exact function of sigma‐1 (σ1) receptors is not yet known, their role in the regulation of intracellular Ca2+ levels and sterol biosynthesis, functions that could be assigned to mitochondria, are the only mechanisms described.
Using preparations of purified rat liver and brain mitochondria we demonstrate herein the presence of σ‐like binding sites. [3H](+)‐pentazocine, a σ1 radioligand was used to label these sites.
In the liver, [3H](+)‐pentazocine labelled one class of binding sites with high affinity (Kd=3 nM), similar to that observed in liver microsomes and synaptic membranes. These sites were located on the outer mitochondrial membranes and displayed high affinity for other σ1 ligands namely, haloperidol, ifenprodil, carbetapentane or 1,3‐di(2‐tolyl)guanidine (DTG).
The presence of σ1 receptors on liver mitochondria was confirmed using double fluorescence immunostaining.
[3H](+)‐pentazocine binding sites were also found on brain mitochondria but they appeared pharmacologically distinct to the liver ones as [3H](+)‐pentazocine and typical σ1 ligands displayed lower affinities for these sites. Nevertheless, [3H](+)‐pentazocine binding on both liver and brain mitochondria was modulated by progesterone, a putative endogenous ligand for σ receptors.
Our data demonstrates the presence of [3H](+)‐pentazocine binding sites with pharmacological characteristics identical to σ1 receptors on rat liver mitochondrial membranes. The pharmacological significance of these sites and their role on mitochondrial function remain unknown.
British Journal of Pharmacology (2002) 135, 1607–1615; doi:
We have evaluated the protective effect of trimetazidine on an animal model of doxorubicin-induced cardiotoxicity and hepatotoxicity. The evaluation of these effects were assessed by several means; tissular distribution of doxorubicin, histological examination, assessment of liver function, and EF LV by scintigraphy that characterizes the originality of this study.
We report a PopPK model for cyclosporine in Tunisian HSCT patients. Bayesian estimation using only three concentrations provides good prediction of cyclosporine exposure. These tools allow us to routinely estimate cyclosporine AUC in a clinical setting.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.