ANTIDEPRESSANTS DIRECTLY INFLUENCE IN-SITU BINDING OF GUANINE-NUCLEOTIDE IN SYNAPTIC MEMBRANE

The present study examined the in vitro effects of antidepressants on functional photoaffinity labeling of GTP binding protein. Saturation b inding studies were performed by incubating membranes with increasing concentrations of [P-32]-AAGTP, followed by UV irradiation and SDS-PAG E. The specifically bound isotherms for each of the G proteins studied showed characteristics of a one site model. Scatchard analysis reveal ed increases in the Bmax and Kd of AAGTP binding for each of the G pro teins (especially stimulatory G proteins) with the addition of antidep ressants such as amitriptyline, clomipramine, desipramine and mianseri n but not with monoamine oxidase inhibitor, antipsychotics and axiolyt ics. These results suggested that drugs having antidepressive properti es may directly affect G protein, especially Gs protein.