[³H]BHDP as a novel and selective ligand for δ1 receptors in liver mitochondria and brain synaptosomes of the rat

Anis Klouz , Jean-Paul Tillement (1) , Marie-Françoise Boussard , Michel Wierzbicki , Vincent Berezowski (2) , Roméo Cecchelli (2) , Serge Labidalle , Brigitte Onteniente , Didier Morin (3)

1 Laboratoire de Pharmacologie
2 LBHE - Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique
3 IMRB - Institut Mondor de Recherche Biomédicale

The binding profile of [3H]BHDP [³H]N-benzyl-N'-(2-hydroxy-3,4-dimethoxybenzyl)-piperazine) was evaluated. [³H]BHDP labelled a single class of binding sites with high affinity (K_d = 2-3 nM) in rat liver mitochondria and synaptic membranes. The pharmacological characterization of these sites using δ reference compounds revealed that these sites are δ receptors and, more particularly, δ1 receptors. Indeed, BHDP inhibited [³H]pentazocine binding, a marker for δ1 receptors, with high affinity in a competitive manner. BHDP is selective for δ1 receptors since it did not show any relevant affinity for most of the other receptors, ion channels or transporters tested. Moreover, in an in vitro model of cellular hypoxia, BHDP prevented the fall in adenosine triphosphate (ATP) levels caused by 24 h hypoxia in cultured astrocytes. Taken together, these results demonstrate that [³H]BHDP is a potent and selective ligand for δ1 receptors showing cytoprotective effects in astrocytes.

Keywords: δ Receptor; Liver mitochondrion; Synaptosome; Binding; Hypoxia; Astrocyte

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology

Anis Klouz, Jean-Paul Tillement, Marie-Françoise Boussard, Michel Wierzbicki, Vincent Berezowski, et al.. [³H]BHDP as a novel and selective ligand for δ1 receptors in liver mitochondria and brain synaptosomes of the rat. FEBS Letters, 2003, 553, p. 157-162. ⟨hal-00537718⟩