Are high-affinity progesterone binding site(s) from porcine liver microsomes members of the σ receptor family?

Abstract

Membrane progesterone binding sites have been purified recently from pig liver. Since progesterone is considered as an endogenous sigma ( σ) receptor ligand, these sites were characterized pharmacologically by ligands selective for σ receptor and dopamine receptor binding sites, and by other drugs from distinct pharmacological classes. Binding studies using the radioligand [ 3H]progesterone were done in crude membrane preparations and solubilized fractions to determine half-maximal inhibitory concentration (IC 50) values, from which inhibitory constants ( K i values) were calculated. Radioligand binding was inhibited by the σ receptor ligands haloperidol, carbetapentane citrate, 1,3-Di(2-tolyl)guanidine (DTG), R(−)- N-(3-phenyl-1-propyl)-1-phenyl-2 aminopropane HCl ( R(−)-PPAAP HCl), or σ receptor antagonists like (+)-3-(3-hydroxyphenyl)- N-propylpiperidine HCl ( R(+)-PPP HCl) and cis-9-[3-(3,5-dimethyl-1-piperazinyl)propyl]-9 H-carbazole dihydrochloride (rimcazole 2HCl). The hierarchy of inhibitory action was not fully compatible with either σ receptor class I (moderate affinity of pentazocine, diphenylhydantoin (phenytoin) insensitivity) or II sites (high affinity of carbetapentane). The data thus suggest that progesterone binding sites in porcine liver membranes are related to the σ receptor binding site superfamily, but may represent a particular species with progesterone specificity.