Altered 5-HT(2A) binding sites and second messenger inositol trisphosphate (IP(3)) levels in hippocampus but not in frontal cortex from depressed suicide victims.
The binding parameters of 5-HT(2A) and levels of its second messenger, 1,4,5-trisphosphate (IP(3)), were simultaneously studied in frontal cortex and hippocampus from the brains of 18 control subjects and 18 depressed suicide victims. All suicides met DSM-III-R criteria for depressive symptoms, suffered a violent death and had not taken any antidepressant drugs for at least 6 months prior to death. A significant decrease in the number of 5-HT(2A) binding sites (154+/-22 vs. 254+/-36 fmol/mg), together with a significantly lower apparent affinity constant (1.02+/- 0.08 vs. 1. 36+/-0.09 nM), was detected in hippocampus but not in frontal cortex from the depressed suicides compared to the control subjects. Furthermore, IP(3) concentrations were significantly increased in hippocampus (3.2+/-0.3 vs. 2.1+/-0.3 pmol/g) but not in frontal cortex (1.3+/-0.3 vs. 2.7+/-0.5 pmol/g) from the suicide victims. The reported results may indicate a significant hypersensitivity of the 5-HT(2A) postsynaptic receptor located in the hippocampus from depressed suicide victims, giving rise to an enhancement of its intracellular signaling system with higher IP(3) production.
Rosel
P
P
Hormone Unit, Department of Clinical Chemistry, CSU Bellvitge, Feixa Llarga s/n, Hospitalet de Llobregat, Barcelona, Spain.
Arranz
B
B
San
L
L
Vallejo
J
J
Crespo
J M
JM
Urretavizcaya
M
M
Navarro
M A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000008:administration & dosage; D001344:Autopsy; D016022:Case-Control Studies; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism*; D015398:Signal Transduction; D013405:Suicide
D000928:Antidepressive Agents; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D015544:Inositol 1,4,5-Trisphosphate