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 binding studies were performed by incubating membranes with increasing concentrations of [32P]-AAGTP, followed by UV irradiation and SDS-PAGE. The specifically bound isotherms for each of the G proteins studied showed characteristics of a one site model. Scatchard analysis revealed increases in the Bmax and Kd of AAGTP binding for each of the G proteins (especially stimulatory G proteins) with the addition of antidepressants such as amitriptyline, clomipramine, desipramine and mianserin but not with monoamine oxidase inhibitor, antipsychotics and axiolytics. These results suggested that drugs having antidepressive properties may directly affect G protein, especially Gs protein.
Ozawa
H
H
Department of Neuropsychiatry, School of Medicine, Sapporo Medical University, Japan.
Katamura
Y
Y
Hatta
S
S
Amemiya
N
N
Saito
T
T
Ohshika
H
H
Takahata
N
N
D000345:Affinity Labels / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001386:Azides / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010761:Phosphorus Radioisotopes; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D013570:Synaptic Membranes / Q000187:drug effects* / Q000378:metabolism*
D000345:Affinity Labels; D000928:Antidepressive Agents; D001386:Azides; D006150:Guanine Nucleotides; D010761:Phosphorus Radioisotopes; C031907:GTP gamma-4-azidoanilide; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins