Direct activation of purified Go-type GTP binding protein by tricyclic antidepressants.
A growing body of evidence suggests that tricyclic antidepressant agents (TCAs) interact with GTP binding proteins (G proteins). We have investigated if TCAs directly alter the function of the purified Go protein which is specifically expressed in neuronal tissue. Several TCAs markedly enhanced the GTPase activity of Go protein in a pertussis toxin-susceptible manner, whereas MAO-inhibitor and anxiolytic agent did not. This enhancing effect of TCAs on Go function may be due to an increase in the GDP-GTP exchange reaction occurring on Go. Thus, it is very likely that TCAs can modify various signal transduction by directly interacting with G proteins in brain cells.
Yamamoto
H
H
Division of Mental Disorder Research, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Tomita
U
U
Mikuni
M
M
Kobayashi
I
I
Kagaya
A
A
Katada
T
T
Ui
M
M
Takahashi
K
K
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001711:Biotransformation / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002417:Cattle; D019204:GTP-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D037342:Pertussis Toxin; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins