2--hydroxy-5-9-dimethyl-2-allyl-6-7-benzomorphan and vanoxerine

In preparation for expression studies for rat brain sigma-binding sites, Xenopus oocytes were tested for the presence of [3H]di-o-tolylguanidine (DTG)-binding sites. Native oocytes were found to contain two intrinsic [3H]DTG-binding sites, a high-affinity site (Kd = 32 +/- 6 nM, Bmax of 45.7 +/- 19 pmol/mg protein) and a low-affinity binding site (Kd = 1.3 +/- 0.7 microM, Bmax of 3.2 +/- 0.7 nmol/mg protein). In a series of radioligand-binding-displacement studies, the high-affinity binding sites were found to have a binding profile which has a similar Kd to that of the mammalian sigma 2-binding site (32 vs. 38 nM). Comparison of the IC50 values for inhibition of [3H]DTG binding in rat liver and oocytes for DTG, haloperidol (HAL), (-)-pentazocine, (+)-3-(3-hydroxyphenyl)-N-propylpiperidine hydrochloride ((+)-3-PPP), (+)-pentazocine and Zn2+, showed similarity in rank (r2 = 0.913) but a 7-fold lower potency in oocytes. These results suggest that the high-affinity [3H]DTG-binding site in oocytes represents a sigma 2-like binding site.

Topics: Animals; Binding Sites; Binding, Competitive; Carbazoles; Dextromethorphan; Female; Guanidines; Haloperidol; Liver; Mazindol; Oocytes; Pentazocine; Phenazocine; Piperazines; Piperidines; Radioligand Assay; Rats; Receptors, sigma; Xenopus laevis; Zinc