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 mouse 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 microM. Maximal effect was almost 10% increase to the control without treatment of drugs. However, another representative agonist, (+)-SKF10,047 showed only a partial activity with maximal effect 5% at 1 microM. NE-100, a representative antagonist, showed no effect at concentrations not more than 100 nM, while it did stimulate GTPase activity at 1 and 10 microM. Furthermore, these stimulative effects of both (+)-pentazocine and SA4503 on GTPase activity were significantly antagonized by NE-100 at 100 nM, suggesting that NE-100 possesses agonist-antagonist property. These findings suggest the possibility that there exist metabotropic sigma receptors.
Tokuyama
S
S
Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, Japan.
Hirata
K
K
Ide
A
A
Ueda
H
H
D000818:Animals; D020558:GTP Phosphohydrolases / Q000187:drug effects; D008024:Ligands; D016015:Logistic Models; D008297:Male; D008566:Membranes / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D017397:Prefrontal Cortex / Q000378:metabolism*; D017480:Receptors, sigma / Q000187:drug effects*; D013268:Stimulation, Chemical
D008024:Ligands; D017480:Receptors, sigma; D020558:GTP Phosphohydrolases