scholarly journals The role of agonistic/antagonistic activity in the development of psychotropic effects of antipsychotics

2019 ◽  
pp. 3-7 ◽  
Author(s):  
V. I. Kozlovskiy ◽  
D. N. Kosterin ◽  
M. Yu. Popov
Keyword(s):  
Neurotransmitter Release ◽  
Dopaminergic System ◽  
Antagonistic Activity ◽  
Psychotic Symptoms ◽  
Dopamine Depletion ◽  
Physiological Mechanisms ◽  
Psychotropic Effects ◽  
Presynaptic Regulation ◽  
Agonistic Effect

The development of psychotic symptoms is traditionally linked to the increase of the functional activity of endogenous dopaminergic system. Antipsychotic effect of existing medications is associated with direct blockade of postsynaptic dopamine receptors. However, direct antagonistic activity is «alien» to physiological mechanisms of neurotransmission modulation, and presynaptic autoreceptor blockade mау produce a reverse (agonistic) effect, enhancing neurotransmitter release. On the other hand, anti-dopamine effect can be achieved by indirect antagonistic activity—by presynaptic dopamine depletion, which is consistent with the natural, physiological mechanisms of reducing neurotransmission. It can be assumed that modulation of presynaptic regulation is one of the promising directions for the development of antipsychotic drugs of future generations.

Effects of metabolized and unmetabolized arachidonate on rat platelet shape change

1984 ◽  
Vol 247 (3) ◽  
pp. H440-H445
Author(s):  
M. G. Lampugnani ◽  
G. de Gaetano
Keyword(s):  
Shape Change ◽  
Antagonistic Activity ◽  
Active Metabolites ◽  
Fatty Acid Molecule ◽  
Lipoxygenase Pathway ◽  
Lipoxygenase Inhibitors ◽  
Agonistic Effect ◽  
Platelet Shape ◽  
Rat Platelets

Arachidonate (0.12-1.5 mM) initiated a concentration-dependent, saturable shape change of rat platelets suspended in citrated plasma. Interaction of arachidonate with platelets led to the formation of active metabolites that appeared to be the actual inducers of shape change. Among these, prostaglandin endoperoxides rather than thromboxane A2 seemed necessary for shape change. No role of the products of the lipoxygenase pathway could be shown. In the presence of cyclooxygenase and lipoxygenase inhibitors, arachidonate (0.25-0.5 mM) prevented platelet shape change induced by the endoperoxide analog U-46619 but not by other agonists such as ADP or serotonin. Arachidonate acts therefore as both an agonist and an antagonist of platelet shape change. The agonistic effect requires arachidonate metabolism while the antagonistic activity seems to be linked to the fatty acid molecule itself.

Questions on the role of biofilms for the adaptation of microorganisms to unfavorable environmental factors by the example of P. aeruginosa

2020 ◽  
Vol 99 (4) ◽  
pp. 379-383
Author(s):  
Vasily N. Afonyushkin ◽  
N. A. Donchenko ◽  
Ju. N. Kozlova ◽  
N. A. Davidova ◽  
V. Yu. Koptev ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Environmental Factors ◽  
Barrier Function ◽  
Infectious Agent ◽  
Antagonistic Activity ◽  
The Body ◽  
Main Function ◽  
Pathogenic Potential ◽  
The Face

Pseudomonas aeruginosa is a widely represented species of bacteria possessing of a pathogenic potential. This infectious agent is causing wound infections, fibrotic cystitis, fibrosing pneumonia, bacterial sepsis, etc. The microorganism is highly resistant to antiseptics, disinfectants, immune system responses of the body. The responses of a quorum sense of this kind of bacteria ensure the inclusion of many pathogenicity factors. The analysis of the scientific literature made it possible to formulate four questions concerning the role of biofilms for the adaptation of P. aeruginosa to adverse environmental factors: Is another person appears to be predominantly of a source an etiological agent or the source of P. aeruginosa infection in the environment? Does the formation of biofilms influence on the antibiotic resistance? How the antagonistic activity of microorganisms is realized in biofilm form? What is the main function of biofilms in the functioning of bacteria? A hypothesis has been put forward the effect of biofilms on the increase of antibiotic resistance of bacteria and, in particular, P. aeruginosa to be secondary in charcter. It is more likely a biofilmboth to fulfill the function of storing nutrients and provide topical competition in the face of food scarcity. In connection with the incompatibility of the molecular radii of most antibiotics and pores in biofilm, biofilm is doubtful to be capable of performing a barrier function for protecting against antibiotics. However, with respect to antibodies and immunocompetent cells, the barrier function is beyond doubt. The biofilm is more likely to fulfill the function of storing nutrients and providing topical competition in conditions of scarcity of food resources.

scholarly journals A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Eder Gambeta ◽  
Maria A. Gandini ◽  
Ivana A. Souza ◽  
Laurent Ferron ◽  
Gerald W. Zamponi
Keyword(s):  
Trigeminal Neuralgia ◽  
Missense Mutation ◽  
Neurotransmitter Release ◽  
Trigeminal System ◽  
Wild Type ◽  
Calcium Dependent ◽  
Whole Cell Patch Clamp ◽  
C Terminus ◽  
Dependent Inactivation

AbstractA novel missense mutation in the CACNA1A gene that encodes the pore forming α1 subunit of the CaV2.1 voltage-gated calcium channel was identified in a patient with trigeminal neuralgia. This mutation leads to a substitution of proline 2455 by histidine (P2455H) in the distal C-terminus region of the channel. Due to the well characterized role of this channel in neurotransmitter release, our aim was to characterize the biophysical properties of the P2455H variant in heterologously expressed CaV2.1 channels. Whole-cell patch clamp recordings of wild type and mutant CaV2.1 channels expressed in tsA-201 cells reveal that the mutation mediates a depolarizing shift in the voltage-dependence of activation and inactivation. Moreover, the P2455H mutant strongly reduced calcium-dependent inactivation of the channel that is consistent with an overall gain of function. Hence, the P2455H CaV2.1 missense mutation alters the gating properties of the channel, suggesting that associated changes in CaV2.1-dependent synaptic communication in the trigeminal system may contribute to the development of trigeminal neuralgia.

scholarly journals Role of miRNAs in Normal Endometrium and in Endometrial Disorders: Comprehensive Review

2021 ◽  
Vol 10 (16) ◽  
pp. 3457
Author(s):  
Kamila Kolanska ◽  
Sofiane Bendifallah ◽  
Geoffroy Canlorbe ◽  
Arsène Mekinian ◽  
Cyril Touboul ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Mirna Expression ◽  
Expression Patterns ◽  
Mirna Regulation ◽  
Rigorous Analysis ◽  
Sexual Hormones ◽  
Physiological Mechanisms ◽  
Normal Endometrium ◽  
Gynecological Disorders

The molecular responses to hormonal stimuli in the endometrium are modulated at the transcriptional and post-transcriptional stages. Any imbalance in cellular and molecular endometrial homeostasis may lead to gynecological disorders. MicroRNAs (miRNAs) are involved in a wide variety of physiological mechanisms and their expression patterns in the endometrium are currently attracting a lot of interest. miRNA regulation could be hormone dependent. Conversely, miRNAs could regulate the action of sexual hormones. Modifications to miRNA expression in pathological situations could either be a cause or a result of the existing pathology. The complexity of miRNA actions and the diversity of signaling pathways controlled by numerous miRNAs require rigorous analysis and findings need to be interpreted with caution. Alteration of miRNA expression in women with endometriosis has been reported. Thus, a potential diagnostic test supported by a specific miRNA signature could contribute to early diagnosis and a change in the therapeutic paradigm. Similarly, specific miRNA profile signatures are expected for RIF and endometrial cancer, with direct implications for associated therapies for RIF and adjuvant therapies for endometrial cancer. Advances in targeted therapies based on the regulation of miRNA expression are under evaluation.

scholarly journals Nanopore-Sequencing Characterization of the Gut Microbiota of Melolontha melolontha Larvae: Contribution to Protection against Entomopathogenic Nematodes?

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 396
Author(s):  
Ewa Sajnaga ◽  
Marcin Skowronek ◽  
Agnieszka Kalwasińska ◽  
Waldemar Kazimierczak ◽  
Karolina Ferenc ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Entomopathogenic Nematodes ◽  
Bacterial Species ◽  
Antagonistic Activity ◽  
Rrna Gene ◽  
Nanopore Sequencing ◽  
Bacterial Phyla ◽  
Melolontha Melolontha

This study focused on the potential relationships between midgut microbiota of the common cockchafer Melolontha melolontha larvae and their resistance to entomopathogenic nematodes (EPN) infection. We investigated the bacterial community associated with control and unsusceptible EPN-exposed insects through nanopore sequencing of the 16S rRNA gene. Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes were the most abundant bacterial phyla within the complex and variable midgut microbiota of the wild M. melolontha larvae. The core microbiota was found to include 82 genera, which accounted for 3.4% of the total number of identified genera. The EPN-resistant larvae differed significantly from the control ones in the abundance of many genera belonging to the Actinomycetales, Rhizobiales, and Clostridiales orders. Additionally, the analysis of the microbiome networks revealed different sets of keystone midgut bacterial genera between these two groups of insects, indicating differences in the mutual interactions between bacteria. Finally, we detected Xenorhabdus and Photorhabdus as gut residents and various bacterial species exhibiting antagonistic activity against these entomopathogens. This study paves the way to further research aimed at unravelling the role of the host gut microbiota on the output of EPN infection, which may contribute to enhancement of the efficiency of nematodes used in eco-friendly pest management.

scholarly journals The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment—A Narrative Review

2021 ◽  
Vol 10 (7) ◽  
pp. 1475
Author(s):  
Waldemar Kryszkowski ◽  
Tomasz Boczek
Keyword(s):  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Glutamate Release ◽  
Molecular Targets ◽  
Brain Regions ◽  
Psychotic Symptoms ◽  
Unknown Etiology ◽  
Metabotropic Glutamate ◽  
G Protein Coupled

Schizophrenia is a severe neuropsychiatric disease with an unknown etiology. The research into the neurobiology of this disease led to several models aimed at explaining the link between perturbations in brain function and the manifestation of psychotic symptoms. The glutamatergic hypothesis postulates that disrupted glutamate neurotransmission may mediate cognitive and psychosocial impairments by affecting the connections between the cortex and the thalamus. In this regard, the greatest attention has been given to ionotropic NMDA receptor hypofunction. However, converging data indicates metabotropic glutamate receptors as crucial for cognitive and psychomotor function. The distribution of these receptors in the brain regions related to schizophrenia and their regulatory role in glutamate release make them promising molecular targets for novel antipsychotics. This article reviews the progress in the research on the role of metabotropic glutamate receptors in schizophrenia etiopathology.

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