SIGMA-LIGANDS STIMULATE GTPASE ACTIVITY IN MOUSE PREFRONTAL MEMBRANES- EVIDENCE FOR THE EXISTENCE OF METABOTROPIC SIGMA-RECEPTOR

We studied effects of various sigma ligands on GTPase activity in mous e prefrontal membranes. Some representative sigma agonists, such as ()-pentazocine, SA4503 and (+)-3-PPP, stimulated the GTPase activity in a concentration-dependent manner in ranges of 10 nM to 10 mu M. Maxim al effect was almost 10% increase to the control without treatment of drugs. However, another representative agonist, (+)-SKF10,047 showed o nly a partial activity with maximal effect 5% at 1 mu M. NE-100, a rep resentative antagonist, showed no effect at concentrations not more th an 100 nM, while it did stimulate GTPase activity at 1 and 10 mu M. Fu rthermore, these stimulative effects of both (+)-pentazocine and SA450 3 on GTPase activity were significantly antagonized by NE-100 at 100 n M, suggesting that NE-100 possesses agonist-antagonist property. These findings suggest the possibility that there exist metabotropic sigma receptors. (C) 1997 Elsevier Science Ireland Ltd.