ARE HIGH-AFFINITY PROGESTERONE BINDING SITE(S) FROM PORCINE LIVER-MICROSOMES MEMBERS OF THE SIGMA-RECEPTOR FAMILY

Membrane progesterone binding sites have been purified recently from p ig liver. Since progesterone is considered as an endogenous sigma (sig ma) receptor Ligand, these sites were characterized pharmacologically by ligands selective for sigma receptor and dopamine receptor binding sites, and by other drugs from distinct pharmacological classes. Bindi ng studies using the radioligand [H-3]progesterone were done in crude membrane preparations and solubilized fractions to determine half-maxi mal inhibitory concentration (IC50) values, from which inhibitory cons tants (K-i values) were calculated. Radioligand binding was inhibited by the sigma receptor ligands haloperidol, carbetapentane citrate, 1,3 -Di(2-tolyl)guanidine (DTG), R(-)-N-(3-phenyl-1-propyl)-1-phenyl-2 ami nopropane HCl (R(-)-PPAAP HCl), or sigma receptor antagonists like (+) -3-(3-hydroxyphenyl)-N-propylpiperidine HCl (R(+)-PPP HCl) and 3-(3,5- dimethyl-1-piperazinyl)propyl]-9H-carbazole dihydrochloride (rimcazole 2HCl). The hierarchy of inhibitory action was not fully compatible wi th either sigma receptor class I (moderate affinity of pentazocine, di phenylhydantoin (phenytoin) insensitivity) or II sites (high affinity of carbetapentane), The data thus suggest that progesterone binding si tes in porcine liver membranes are related to the sigma receptor bindi ng site superfamily, but may represent a particular species with proge sterone specificity. (C) 1998 Elsevier Science B.V.