Contemporary society is characterized by rapid changes. Various epidemiological, political and economic crises represent a burden to mental health of nowadays population, which may at least partially explain the increasing incidence of mental disorders, including schizophrenia. Schizophrenia is associated with premature mortality by at least 13-15 years. The leading cause of premature mortality in schizophrenia patients is high incidence of cardiovascular diseases. The specific-cause mortality risk for cardiovascular diseases in schizophrenia patients is more than twice higher as compared to the general population. Several factors are discussed as the factor of cardiovascular diseases development. Intensive efforts to identify possible link between schizophrenia and cardiovascular diseases are made. It seems that sigma 1 receptor may represent such link. By modulation of the activity of several neurotransmitter systems, including dopamine, glutamate, and GABA, sigma 1 receptor might play a role in pathophysiology of schizophrenia. Moreover, significant roles of sigma 1 receptor in cardiovascular system have been repeatedly reported. The detailed role of sigma 1 receptor in both schizophrenia and cardiovascular disorders development however remains unclear. The article presents an overview of current knowledge about the association between schizophrenia and cardiovascular diseases and proposes possible explanations with special emphasis on the role of the sigma 1 receptor.

• MeSH
• kardiovaskulární nemoci * diagnóza   epidemiologie   MeSH
• kardiovaskulární systém * MeSH
• lidé MeSH
• schizofrenie * diagnóza   epidemiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Haloperidol is an antipsychotic agent that primarily acts as an antagonist of D2 dopamine receptors. Besides other receptor systems, it targets sigma 1 receptors (σ1Rs) and inositol 1,4,5-trisphosphate receptors (IP3Rs). Aim of this work was to investigate possible changes in IP3Rs and σ1Rs resulting from haloperidol treatment and to propose physiological consequences in differentiated NG-108 cells, i.e., effect on cellular plasticity. Haloperidol treatment resulted in up-regulation of both type 1 IP3Rs (IP3R1s) and σ1Rs at mRNA and protein levels. Haloperidol treatment did not alter expression of other types of IP3Rs. Calcium release from endoplasmic reticulum (ER) mediated by increased amount of IP3R1s elevated cytosolic calcium and generated ER stress. IP3R1s were bound to σ1Rs, and translocation of this complex from ER to nucleus occurred in the group of cells treated with haloperidol, which was followed by increased nuclear calcium levels. Haloperidol-induced changes in cytosolic, reticular, and nuclear calcium levels were similar when specific σ1 blocker -BD 1047- was used. Changes in calcium levels in nucleus, ER, and cytoplasm might be responsible for alterations in cellular plasticity, because length of neurites increased and number of neurites decreased in haloperidol-treated differentiated NG-108 cells.

• Klíčová slova
• BD 1047, Dopamine 2 receptor, Haloperidol, Inositol 1,4,5-trisphosphate receptor, NG-108 cells, Sigma 1 receptor,
• MeSH
• antipsychotika farmakologie   MeSH
• buněčná diferenciace účinky léků   fyziologie   MeSH
• haloperidol farmakologie   MeSH
• inositol-1,4,5-trisfosfát - receptory metabolismus   MeSH
• krysa rodu Rattus MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• neuroplasticita účinky léků   fyziologie   MeSH
• receptor sigma-1 MeSH
• receptory sigma metabolismus   MeSH
• vazba proteinů účinky léků   fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antipsychotika MeSH
• haloperidol MeSH
• inositol-1,4,5-trisfosfát - receptory MeSH
• Itpr1 protein, rat MeSH Prohlížeč
• receptory sigma MeSH