Abstract: Brain endocannabinoid system is proposed to play a role in the pathogenesis of affective disorders. In the present study, we analyzed the functionality of the cannabinoid receptor type 1 (CB1 receptor) at different transduction levels in prefrontal cortex (PFC) of depressed suicide victims. We examined stimulation of [35S]GTP?S binding, activation of G? protein subunits and inhibition of adenylyl cyclase by the cannabinoid agonist WIN55,212-2, as well as [3H]CP55,940 binding, in PFC homogenates from suicide victims with major depression (MD) and matched control subjects. CB1 receptor-stimulated [35S]GTP?S binding was significantly greater in the PFC of MD compared with matched controls (23%, p?0.05). This increase was most evident in the PFC from MD subgroup with negative blood test for antidepressants (AD) at the time of death (AD-free) (38%, p?0.05), being absent when comparing the AD-treated MD cases with their controls. The density of CB1 receptors and their coupling to adenylyl cyclase were similar between MD and control cases, regardless of the existence of AD intake. Analysis of [35S]GTP?S-labelled G? subunits allowed for the detection of upregulated CB1 receptor coupling to G?o, but not to G?i1, G?i2, G?i3, G?z subunits, in the PFC from AD-free MD suicides. These results suggest that increased CB1 receptor functionality at the G?i/o protein level in the PFC of MD subjects is due to enhanced coupling to G?o proteins and might be modulated by AD intake. These data provide new insights into the role of endocannabinoid neurotransmission in the pathobiology of MD and suggest its regulation by ADs.
Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria
Fuente: Biochem Pharmacol. 2018 Nov;157:258-265
Fecha de publicación: 01/11/2018
Nº de páginas: 8
Tipo de publicación: Artículo de Revista
Proyecto español: SAF2007/61862 ; SAF2011-25020 ; SAF2015-67457-R ; SAF 2009-
Url de la publicación: https://dx.doi.org/10.1016/j.bcp.2018.08.012