Dietetics, Nutrition and Biological Sciences
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Item The Roles of Opioid Receptors and Agonists in Health and Disease Conditions(Maxwell Scientific Organization,, 2011-04-30) Ibegbu, A. O.; Mullaney, I.; Fyfe, Lorna; McBean, DouglasOpioid receptors are found in the Central Nervous System (CNS) and are classified as mu (µ), kappa (κ), delta (δ) and sigma (σ) opioid receptors. Opioid receptors belong to the large family of G Protein Coupled Receptors (GPCRs), and have diverse and important physiological roles. The aim of the present review is to discuss the roles played by opioid receptors, their agonists and antagonists in health and disease conditions. Opioid receptors are not uniformly distributed in the CNS and are found in areas concerned with pain, with the highest concentration in the cerebral cortex, followed by the amygdala, septum, thalamus, hypothalamus, midbrain and spinal cord. Activated delta opioid receptors are coupled to Gi1 while activated mu opioid receptors are coupled to Gi3 in neuroblastoma cells. Mu opioid receptors are activated by mu receptor agonists and are coupled through the Gi1 and GoA. Both mu and kappa opioid receptors are coupled via both Gi and Gz and opioid receptors are important targets for thousands of pharmacological agents. GPCRs typically require activation by agonists for their signalling activity to be initiated but some of the GPCRs may display basal or spontaneous signalling activity in the absence of an agonist. The stimulation of these receptors triggers analgesic effects and affects the function of the nervous system, gastrointestinal tract and other body systems. Hundreds of analogs of opioid peptides have been synthesized in an effort to make the compounds more active, selective, and resistant to biodegradation than the endogenous ligands. All these modifications resulted in obtaining very selective agonists and antagonists with high affinity at mu-, delta-, and kappa-opioid receptors, which are useful in further studies on the pharmacology of opioid receptors in a mammalian organism.Item The Effect of Hypoxia on G Protein Coupled (Opioid) Receptor Gene Expression in Cortical B50 Neurons in Culture(Maxwell Scientific Organization,, 2011-04-30) Ibegbu, A. O.; Mullaney, I.; Fyfe, Lorna; McBean, DouglasHypoxia adversely affects cells and tissues, and neuronal cells in particular have been shown to be more susceptible to the injurious effects of hypoxia in which they may begin to die when oxygen supply is reduced or completely eliminated. Opioid receptor agonists have been shown to elicit several central nervous system effects, mediated via G protein-coupled receptors. The aim of this study was to study the effect of hypoxia on G protein coupled receptor gene expression using mu opioid receptor as a case study in cortical neuronal B50 cell lines in culture. The B50 cells were cultured in normoxia (21% O2; 5% CO2) and hypoxia (5% O2; 5% CO2), and were treated with opioid agonists to determine their effects on hypoxia-induced changes. Three opioid agonists {DAMGO(_), DSLET(*) and ICI--199,441(6)}, were administered to the cells as treatment for 48 hours after 48 hours of initial culture for a total of 96 hours of culture in hypoxic conditions at concentrations of 10, 50 and 100 :M. The levels of G-protein coupled receptor (mu opioid) mRNAs were assessed using RT-PCR. The results showed that hypoxia induced morphological changes in B50 cells in hypoxia while the mu opioid RT-PCR mRNA levels showed no appreciable changes in normal, hypoxic and treated cells. The results show that B50 neuronal cells are susceptible to damage and injurious effects of hypoxia, as are most brain cells and the opioid agonist treatments showed there were no changes in the level of mu opioid receptor gene expression due to hypoxia or agonist treatment in neuronal B50 cells in culture.Item The Effect of Hypoxia on G Protein Coupled (CB1) Receptor Gene Expression in Cortical B50 Neurons in Culture(Maxwell Scientific Organization,, 2011-02-10) Ibegbu, A. O.; Mullaney, I.; Fyfe, Lorna; McBean, DouglasHypoxia adversely affects cells and tissues, and neuronal cells in particular have been shown to be more susceptible to the injurious effects of hypoxia in which they may begin to die when oxygen supply is reduced or completely eliminated. Cannabinoid (CB1) receptor agonists have been shown to elicit several Central Nervous System (CNS) effects, mediated via G protein-coupled receptors. The aim of this study was to examine the effect of hypoxia on G protein coupled receptor (CB1) gene expression in cortical neuronal B50 cell lines in culture. The B50 cells were cultured in normoxia (21% O2; 5% CO2) and hypoxia (5% O2; 5% CO2), and were treated with cannabinoid agonists to determine their effects on hypoxia-induced changes. Three cannabinoid agonists [Win55,212-2 mesylate (Win), arachidonoylethanolamide (AEA) and 2- arachidonylglycerol (2-AG)], were administered to the cells as treatment for 48 hours after 48hours of initial culture for a total of 96hours of culture in hypoxic conditions at concentrations of 10, 50 and 100 nM. The levels of G-protein coupled receptor (CB1) mRNAs were assessed using RT-PCR. The results showed that hypoxia induced morphological changes in B50 cells in hypoxia while the CB1 RT-PCR mRNA levels showed no appreciable changes in normal, hypoxic and treated cells. The results show that B50 neuronal cells are susceptible to damage and injurious effects of hypoxia, as are most brain cells and the cannabinoid agonist treatments showed there were no changes in the level of CB1 receptor gene expression due to hypoxia or agonist treatment in neuronal B50 cells in culture.Item Oxidative stress does not predispose neuronal cells to changes in G protein coupled (opioid) receptor gene expression in cortical B50 neurons in culture(Kamla-Raj Enterprises, 2012-12) Ibegbu, A. O.; Mullaney, I.; Fyfe, Lorna; McBean, DouglasOxidative stress adversely affects neuronal cells in which they may die when oxygen supply is reduced or eliminated and opioid receptor agonists elicit several central nervous system effects. The aim of this study was to evaluate the effect of oxidative stress on opioid receptor gene expression in cortical B50 cells. The cells were cultured in normoxia, hypoxia and treated with opioid agonists; DAMGO (_), DSLET () and ICI-199,441 () for 48 hours after 48 hours of initial culture at dose of 10_M, 50_M and 100_M. The level of mu opioid receptor mRNA was assessed using RT-PCR. The results show that oxidative stress induced changes in B50 cells in hypoxia while mu opioid mRNA levels showed no change. The results show that B50 cells are susceptible to damage by oxidative stress and opioid agonist treatments showed no change in the level of mu opioid receptor gene expression in B50 cells. Kamla-Raj 2012.Item The Roles of Guanine Nucleotide Binding Proteins in Health and Disease(Maxwell Scientific Organization,, 2011-02-10) Ibegbu, A. O.; Mullaney, I.; Fyfe, Lorna; McBean, DouglasG-proteins are important mediators of cellular and tissue functions and are characterised by a recognition site for Guanine Triphosphate (GTP), Guanine Diphosphate (GDP) and possess intrinsic GTPase activity. They play important roles in signal transduction responsible for cytoskeletal remodelling, cellular differentiation and vesicular transport. They are made up of three types namely, the small G-proteins, the sensors and the heterotrimeric G-proteins. The G-protein heterotrimers consist of G-alpha (G), G-beta (G$) and G-gamma (G() subunits. Each heterotrimeric G-protein have different subunits and the combination of these subunits define the specific role of each G-protein. The activation of G subunits regulates the activity of effector enzymes and ion channels while G$( subunits function in the regulation of mitogen-activated protein kinase (MAP-kinase) pathway. The G-protein-mediated signal transduction is important in the regulation of a cells morphological and physiological response to external stimuli. MAPKs are involved in the phosphorylation of transcription factors that stimulate gene transcription. Gs stimulates adenylate cyclase, thereby increasing cyclic adenosine monophosphate (cAMP) leading to the phosphorylation and subsequent activation of Ca_+ channels. G proteins are involved in disease pathology through several mechanisms which interfere with the G protein activity. Other disease pathologies associated with abnormal mutations in G proteins can interfere with signal transduction pathways which may involve signal transmission that is either excessive, by augmentation of G protein function, or insufficient, via inactivation of G proteins.Item Oxidative stress-induced effects on pattern and pattern formation in cortical B50 neuronal cells in culture(2013-11) Ibegbu, A. O.; Fyfe, Lorna; McBean, Douglas; Mullaney, I.Oxidative stress adversely affects cells and tissues, and neuronal cells in particular have been shown to be more susceptible to the injurious effects of oxidative stress in which the cells may die when oxygen supply is reduced or completely eliminated. The aim of the present study was to study the effect of oxidative stress using hypoxia as a bench mark on the morphology of B50 neuronal cell lines cultured in hypoxia using neuronal pattern and pattern formation as case study. The B50 cells were cultured in normal incubator (21%O2; 5% CO2) as control group and hypoxic incubator (5%O2; 5% CO2) as the experimental group. Neuronal morphology, pattern and wellbeing were assessed using same field morphological assessment of cells and lactate dehydrogenase leakage (LDH). The result showed groups of dead and degenerating B50 neuronal cells, altered neuronal pattern and pattern formation and some significant changes (P<0.05) in cellular levels of LDH leakage in normal B50 cells and hypoxic cells. The changes in morphology, neuronal pattern and LDH release indicate that oxidative stress has induced morphological and cellular changes in cortical B50 cells in culture and that the B50 neuronal cells are susceptible to damage and injurious effects of oxidative stress represented by hypoxia as most brain cells.Item The Effects of Hypoxia and Opioid Receptor Agonists Treatment in Cortical B50 Neuronal Cells in Culture(Uludag University Applied Research Center for Agriculture (ARCA) and Applied Research Center for Environmental Problems (ARCEP), Uludag University Gorukle Campus, 16059 Bursa-Turkey, 2012-12) Ibegbu, A. O.; Fyfe, Lorna; McBean, Douglas; Mullaney, I.Hypoxia has been implicated in nerve cell deaths in many neurological disorders and opioid receptor agonists have some positive benefits on the nervous system. The aim of the present work was to investigate the effects of hypoxia and opioid receptor agonists' treatment on the morphology of B50 cells cultured in hypoxia using neuronal pattern and pattern formation as a case study. The B50 cells were cultured in normal incubator (21%O2; 5% CO2) as the control group and hypoxic incubator (5%O2; 5% CO2) as the experimental group and three opioid receptor agonists namely DAMGO (_), DSLET () and ICI-199,441 () were administered to the cells for 48 hours as treatment against hypoxia after 48 hours of culture at 10_M, 50_M and 100_M concentrations. Neuronal morphology and wellbeing was assessed using same field morphological assessment and lactate dehydrogenase leakage (LDH). The result showed groups of dead and degenerating B50 neuronal cells, altered neuronal pattern and pattern formation and some significant changes (P<0.05) in cellular levels of LDH leakage in normal, hypoxic cells and cells treated with different agonists. The changes in morphology, neuronal pattern and LDH release indicate that hypoxia induced morphological and cellular changes in B50 cells in hypoxia and opioid agonists have some potential benefits in the treatment of hypoxia-induced changes in B50 cells in culture.Item The Roles of G-protein coupled receptors in health and disease conditions(2012-04-01) Ibegbu, A. O.; Mullaney, I.; Fyfe, Lorna; McBean, DouglasThe super family of G-protein-coupled receptors (GPCRs) is the main target for the actions exerted by hormones, drugs and neurotransmitters. Each GPCR shows preferential coupling to some members of the G-protein family such as Gs, Gi and Gq which in turn activates the defined second messenger pathways. The G protein-coupled receptors (GPCRs) represent 50-60% of the current drug targets and this family of membrane proteins plays a crucial role in drug discovery, health and disease conditions. The G-protein-mediated signalling system has been used to study transmembrane signalling mechanisms in eukaryotic organisms resulting in different cellular activities and effects such as cellular growth, proliferation and differentiation. The G-protein-mediated signalling systems are made up of three main components, the receptors, the heterotrimeric G-proteins and the effectors in addition to various proteins that modulate the G-protein-mediated signalling process like the regulators of G-protein signalling (RGS) proteins. Mammalian cells express many GPCRs and several types of heterotrimeric G-proteins and their effectors. A number of drugs based on GPCRs have been developed for such different indications as cardiovascular, metabolic, neurodegenerative, psychiatric, and oncologic diseases. Most neurotransmitters of the central nervous system (CNS) act on GPCRs to mediate different cellular responses in normal and disease states. The activation of receptors that interact through Gi e.g. cannabinoid receptor types convey neuronal protection against hypoxic insult and resultant excitotoxic deathItem Morphological changes induced by opioid receptor agonist treatment of B50 neuronal cells cultured in hypoxia(Brazilian Society of Anatomy and, 2013-04) Ibegbu, A. O.; McBean, Douglas; Fyfe, Lorna; Mullaney, I.Introduction: Hypoxia has been implicated in nerve cell deaths that occur in a variety of neurological disorders. Opioid receptor agonists have been shown to have some positive benefits on the nervous system. The aim of the present work was to investigate the effects of hypoxia and opioid receptor agonists' treatment on the morphology of B50 neuronal cell lines cultured in hypoxia. Materials and Methods: The B50 cells were cultured under normoxic conditions (21%O2; 5% CO2) as the control group and under hypoxic conditions (5%O2; 5% CO2) as the experimental group. Three opioid receptor agonists namely DAMGO (_) DSLET () and ICI-199,441 () were administered to the cells for 48 hours as treatment against hypoxia after 48 hours of culture at doses of 10 _M, 50 _M and 100 _M respectively. Neuronal morphology, viability, proliferation and differentiation were assessed using same field morphological assessment. In addition lactate dehydrogenase (LDH) leakage, cellular proliferation and DbcAMP induced differentiation were also assessed. _ opioid receptor mRNA was assessed using RT-PCR. Results: The results showed groups of dead and degenerating B50 neuronal cells and some significant changes (P<0.05) in cellular proliferation, viability cellular differentiation. The levels of LDH leakage showed normal B50 cells (100%), hypoxic cells (587%), and treated cells with 100 _M DAMGO (_) (143%), 50 _M DSLET () (140%) and 50 _M ICI-199,441 () (109%). The changes in morphology, LDH release, neuronal viability, proliferation and differentiation were shown to be dose-dependent between treated hypoxic B50 neurons in culture. Conclusion: The results indicate that opioid agonists have some potential benefits in the treatment of hypoxia-induced changes in neuronal B50 cells in culture.