Functional activation of G(alpha)_q proteins coupled with 5-HT_2A and M₁ muscarinic acetylcholine receptor in prefrontal cortical membranes from suicide victims

Abstract

Suicide is a major public health concern and often associated with mental disorders, such as depression, bipolar illness, and schizophrenia. Although psychosocial stressors are major risk factors of suicide behavior, abnormalities in neurobiological mechanisms have been supposed to be another risk factor. In the present study, functional coupling of G(alpha)_q proteins with 5-HT_2A receptor and M₁ muscarinic acetylcholine receptor (mAChR) was determined by means of [³⁵S]GTPγS binding/immunoprecipitation assay in postmortem human brain membranes, and the effects of suicide on these measures were evaluated. Postmortem human brains were obtained from 20 patients with bipolar disorder, 20 depression, 20 schizophrenia, and 20 control subjects, and the patients groups included suicide victims in 14, 17, and 10 subjects, respectively. When these 80 subjects were divided into suicide victims (n = 41) and non-suicide (n = 39), there were no significant differences in %E_max, pEC₅₀, and slope factor values for each of the two measures between them. Our results indicate that 5-HT_2A receptor- and M₁ mAChR-mediated signaling through G(alpha)_q proteins is unaltered in suicide victims.