British journal of pharmacology
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Cannabis is one of the most widely used illicit drugs among adolescents, and most users first experiment with it in adolescence. Adolescence is a critical phase for brain development, characterized by neuronal maturation and rearrangement processes, such as myelination, synaptic pruning and dendritic plasticity. ⋯ In this review, we outline recent research into the endocannabinoid system focusing on the relationships between adolescent exposure to cannabinoids and increased risk for certain neuropsychiatric diseases such as schizophrenia, as highlighted by both human and animal studies. Particular emphasis will be given to the possible mechanisms by which adolescent cannabis consumption could render a person more susceptible to developing psychoses such as schizophrenia.
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Increased circulating levels of L-alpha-lysophosphatidylinositol (LPI) are associated with cancer and LPI is a potent, ligand for the G-protein-coupled receptor GPR55. Here we have assessed the modulation of breast cancer cell migration, orientation and polarization by LPI and GPR55. ⋯ LPI and GPR55 play a role in the modulation of migration, orientation and polarization of breast cancer cells in response to the tumour microenvironment.
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Natural and synthetic cannabinoids (CBs) induce deleterious or beneficial actions on neuronal survival. The Fas-associated protein with death domain (FADD) promotes apoptosis, and its phosphorylated form (p-FADD) mediates non-apoptotic actions. The regulation of Fas/FADD, mitochondrial apoptotic proteins and other pathways by CB receptors was investigated in the mouse brain. ⋯ CB(1) receptors appear to exert a modest tonic activation of Fas/FADD complexes in brain. However, chronic CB(1) receptor stimulation decreased pro-apoptotic FADD and increased non-apoptotic p-FADD. The multifunctional protein FADD could participate in the mechanisms of neuroprotection induced by CBs.
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The activation of CB(2) receptors induces analgesia in experimental models of chronic pain. The present experiments were designed to study whether the activation of peripheral or spinal CB(2) receptors relieves thermal hyperalgesia and mechanical allodynia in two models of bone cancer pain. ⋯ Spinal CB(2) receptors are involved in the antiallodynic effect induced by AM1241 in two neoplastic models while peripheral and spinal receptors participate in the antihyperalgesic effects. Both effects were mediated by endogenous opiates. The use of drugs that activate CB(2) receptors could be a useful strategy to counteract bone cancer-induced pain symptoms.
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The volatile anaesthetic isoflurane protects the heart from ischaemia and reperfusion (I/R) injury when applied at the onset of reperfusion [anaesthetic postconditioning (APoC)]. However, the mechanism of APoC-mediated protection is unknown. In this study, we examined the effect of APoC on mitochondrial bioenergetics, mitochondrial matrix pH (pH(m)) and cytosolic pH (pH(i)), and intracellular Ca(2+). ⋯ At reperfusion, APoC inhibited mitochondrial respiration, depolarized mitochondria and acidified pH(m). These events may lead to inhibition of mPTP opening and, consequently, to preserved DeltaPsi(m) and ATP synthesis. This reduces intracellular Ca(2+) overload and cell death.