- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
This review summarizes past and recent findings related to corticotropin releasing hormone (CRH, CRF) regulation and its involvement in the neuroendocrine, au-tonomic and behavioral stress reaction. CRH belongs to a larger family of neuropeptides that also includes uro-cortins with different affinity toward the two types of CRH receptors, CRH-R1 and CRH-R2. The new advances in the knowledge of mechanisms of CRH and its receptor sub-types effects show an involvement of CRH in stress and stress-related disorders, such as depression, anxiety and other psychiatric and physic diseases. This review lists some ligands and new drugs that act as agonists and anta-gonists on CRH receptor subtypes. Recent studies open up new possibilities for finding antidepressants that would also influence defensive stress mechanisms. Because CRH receptors are also located in the periphery, the use of CRH antagonists can have therapeutic potential in the treatment and prevention of organic diseases. Mainly non-peptide antagonists that have a potential for the therapeutic use in psychiatric, behavioral and other disorders are prospective in this respect. The aim of the current research is to find non-peptide ligands that penetrate the cerebrospinal barrier and, by binding to the respective CRH receptor, will have an anti-stress effect.
- MeSH
- adrenokortikotropní hormon * antagonisté a inhibitory chemie terapeutické užití MeSH
- lidé MeSH
- neuropeptidy terapeutické užití MeSH
- psychický stres MeSH
- výzkum MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
The neuropeptide galanin is a widely distributed neurotransmitter/neuromodulator that regulates a variety of physiological processes and also participates in the regulation of stress responses. The effect of stress is dependent on the activity of the hypothalamic-adenohypophyseal-adrenal axis. Although the adenohypophysis is a crucial part of this axis, galanin peptides and their receptors have not yet been identified in this part of the pituitary after activation of the stress response. Since there are many controversies about the occurrence of individual galanin receptor subtypes in the adenohypophysis under basal conditions, we decided to verify their presence immunohistochemically, and we clearly demonstrated that the adenohypophysis expresses neuropeptides galanin, galanin-like peptide, and subtypes of galanin receptors GalR1, GalR2 and GalR3. The specificity of the reactions was confirmed by Western blots for galanin receptors. Using real-time qPCR we also demonstrated the presence of three GalR subtypes, with the highest expression of GalR2. In addition, we tested the effect of stress. We found that acute stress did not induce any changes in the GalR2 expression, but increased expression of GalR1 and decreased that of GalR3. We confirmed the involvement of the galanin system in the stress regulation in the adenohypophysis.
- MeSH
- adenohypofýza metabolismus MeSH
- galanin metabolismus MeSH
- imunohistochemie MeSH
- krysa rodu rattus MeSH
- messenger RNA metabolismus MeSH
- receptor galaninu typ 1 metabolismus MeSH
- receptor galaninu typ 2 metabolismus MeSH
- receptor galaninu typ 3 metabolismus MeSH
- receptory galaninové metabolismus MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The multitalented neuropeptide galanin was first discovered 30 years ago but initially no biologic activity was found. Further research studies discovered the presence of galanin in the brain and some peripheral tissues, and galanin was identified as a modulator of neurotransmission in the central and peripheral nervous system. Over the last decade there were performed very intensive studies of the neuronal actions and also of nonneuronal actions of galanin. Other galanin family peptides have been described, namely galanin, galanin-like peptide, galanin-message associated peptide and alarin. The effect of these peptides is mediated through three galanin receptors subtypes, GalR1, GalR2 and GalR3 belonging to G protein coupled receptors, and signaling via multiple transduction pathways, including inhibition of cyclic AMP/protein kinase A (GalR1, GalR3) and stimulation of phospholipase C (GalR2). This also explains why one specific molecule of galanin can be responsible for different roles in different tissues. The present review summarizes the information currently available on the relationship between the galaninergic system and known pathological states. The research of novel galanin receptor specific agonists and antagonists is also very promising for its future role in pharmacological treatment. The galaninergic system is important target for current and future biomedical research.
- MeSH
- buněčná membrána metabolismus patologie MeSH
- galanin fyziologie MeSH
- lidé MeSH
- mozek metabolismus patologie MeSH
- neurony metabolismus patologie MeSH
- receptory galaninové fyziologie MeSH
- sekundární struktura proteinů MeSH
- signální transdukce fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Neuropeptide galanin, galanin-like peptide and galanin receptors 1, 2 and 3 are a crucial part of the so-called galaninergic system. Our previous studies have shown the possible role of this system in mood modulation, especially regarding stress. So far, the galanin receptors have been found in different tissues including brain and heart. Our study deals with changes in expression of galanin receptor subtypes in the heart of Wistar rats exposed to three different types of stress. Galanin receptor subtypes were determined in fluorescently labelled samples using specific primary antibodies, and all sections were analysed in an immunofluorescent microscope and microphotographs. Image analyses were subsequently performed by software ImageJ, using the threshold method with calculation of the DAPI/galanin receptor signal ratio. We found all three types of receptors in the right and left atria and left and right ventricles. Changes in the density of galanin receptors after application of the stressor depended on the observed heart compartment. We found a significant decrease of galanin receptor 1 in all compartments after all types of stress. For GalR2 and GalR3, the increase/decrease of density was dependent on the tested compartment. These results show that galanin receptors could be involved in the function of heart during the cardiac cycle.
- MeSH
- fyziologický stres fyziologie MeSH
- galanin metabolismus MeSH
- indoly farmakologie MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- receptory galaninové metabolismus MeSH
- signální transdukce účinky léků MeSH
- specificita protilátek MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
This review focuses on the research and new discoveries of signaling processes and on the importance of a remarkable system of G protein-coupled receptors (GPCR). GPCRs are the largest and the most diverse family of receptors involved in many physiological processes and represent attractive targets for pharmacological intervention to modify these processes in normal and pathological states. The new knowledge of the regulation of GPCR signaling enabled the synthesis of novel ligands with therapeutic use. Recipients of the 2012 Nobel Prize in chemistry, R. Lefkowitz and B. Kobilka, played a key role in the study of GPCR, arrestins, G-protein-coupled receptor kinases, and ligands functions, as a universal mechanism of receptor action and a molecular understanding of overall GPCR signaling. Their crystallographic studies of ligand-activated GPCRs allowed them to acquire the three-dimensional structures for a number of pharmacologically important receptors. Detailed analysis of the structure of GPCRs allowed the authors to create drug compounds with greater specificity of action and with reduced side effects, the drugs with therapeutic effects.
- MeSH
- lidé MeSH
- mapování interakce mezi proteiny MeSH
- objevování léků MeSH
- proteiny RGS * MeSH
- receptory spřažené s G-proteiny * MeSH
- výzkum MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Tong Luo Jiu Nao (TLJN), a modern formula of traditional Chinese medicine, has proven to be clinically efficacious in several vascular cerebral diseases but its specific effect is not known. In the present study we investigated the acute and persisting effects of TLJN on anxiety model in Wistar male rats. TLJN was administered intragastrically during three successive days (Days 1–3) and then, the double TLJN dose was given on Day 7. For the evaluation of anxiety-related behavior of animals, we used the open field (OF) and elevated plus maze (EPM) paradigms. Testing in the OF was performed on Days 1, 2, 3, 4, 8, 14 and 22; in the EPM on the Day 23. Two-way repeated-measures ANOVA revealed significant differences between control and TLJN treated animals in the open field model where TLJN induced increased exploratory activity, indicating reduced anxiety-like behavior. The effect persisted for several days after the treatment and was still present on Days 14 and 22. Reduced anxiety-like behavior was also observed on EPM 16 days after the last TLJN administration. The results demonstrate behavioral effects of intragastric administered TLJN, which indicate reduced anxiety. Persistence of the induced behavioral changes suggests prolonged duration of action.
- MeSH
- behaviorální symptomy klasifikace MeSH
- bludiště - učení MeSH
- cerebrovaskulární poruchy farmakoterapie MeSH
- chování zvířat účinky léků MeSH
- Gardenia MeSH
- Panax notoginseng MeSH
- potkani Wistar MeSH
- rostlinné extrakty * aplikace a dávkování MeSH
- tradiční čínská medicína * MeSH
- úzkostné poruchy * farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
