Cellular Sites of Action

2015 ◽  
pp. 70-97
Keyword(s):  
Sites Of Action

METABOLISM AND MODE OF ACTION OF ANDROGENS IN TARGET TISSUES OF MALE RATS

1972 ◽  
Vol 69 (1) ◽  
pp. 165-173 ◽  
Author(s):  
H. Schmidt ◽  
I. Noack ◽  
K. D. Voigt
Keyword(s):  
Cell Proliferation ◽  
Cell Metabolism ◽  
Seminal Vesicles ◽  
Male Rats ◽  
Ventral Prostate ◽  
Nucleic Acid Content ◽  
The Difference ◽  
Independent Effects ◽  
Sites Of Action ◽  
Peripheral Metabolism

ABSTRACT The effect of testosterone and 5α-dihydrotestosterone on protein and nucleic acid content as well as on the activities of some enzymes has been studied in the ventral prostate and the seminal vesicles of immature castrated rats. Both androgens were given intraperitoneally in doses of 1 mg daily for one or three days the rats were sacrificed one day after the last injection. In the prostate it was found that 5α-dihydrotestosterone had a greater effect on DNA increase, i. e. cell proliferation than testosterone, whereas cell metabolism was stimulated by the two androgens to nearly the same extent. In the seminal vesicles a single dose led to the same results as had been obtained in the prostate, i. e. a greater cell proliferative action of 5α-dihydrotestosterone and an equal stimulation of cell metabolism by testosterone and 5α-dihydrotestosterone was also observed. When three doses of the two androgens were given, cell proliferation as well as cell metabolism in the seminal vesicles were significantly more increased after 5α-dihydrotestosterone than after testosterone. The difference of action after systemic administration of the two androgens is explained by their different accumulation and by their different peripheral metabolism in the target tissues. From the partly independent effects of various androgens on cell proliferation and cell metabolism the conclusion may be drawn that there exist at least two intracellular sites of action.

An Insight in Pathophysiological Mechanism of Alzheimer’s Disease and its Management using Plant Natural Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Zeba Firdaus ◽  
Tryambak Deo Singh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Natural Products ◽  
Side Effects ◽  
Neuronal Degeneration ◽  
Acetylcholinesterase Inhibitor ◽  
Pathophysiological Mechanism ◽  
Limited Effectiveness ◽  
Drug Development Research ◽  
Sites Of Action

: Alzheimer’s disease (AD) is an age-associated nervous system disorder and a leading cause of dementia worldwide. Clinically it is described by cognitive impairment, and pathophysiologically by deposition of amyloid plaques and neurofibrillary tangles in the brain and neurodegeneration. This article reviews the pathophysiology, course of neuronal degeneration, and the various possible hypothesis of AD progression. These hypotheses include amyloid cascade, tau hyperphosphorylation, cholinergic disruption, metal dysregulation, vascular dysfunction, oxidative stress, and neuroinflammation. There is an exponential increase in the occurrence of the AD in recent few years that indicate an urgent need to develop some effective treatment. Currently, only 2 classes of drugs are available for AD treatment namely acetylcholinesterase inhibitor and NMDA receptor antagonist. Since AD is a complex neurological disorder and these drugs use a single target approach, alternatives are needed due to limited effectiveness and unpleasant side-effects of these drugs. Currently, plants have been used for drug development research especially because of their multiple sites of action and fewer side effects. Uses of some herbs and phytoconstituents for the management of neuronal disorders like AD have been documented in this article. Phytochemical screening of these plants shows the presence of many beneficial constituents like flavonoids, triterpenes, alkaloids, sterols, polyphenols, and tannins. These compounds show a wide array of pharmacological activities such as anti-amyloidogenic, anticholinesterase, and antioxidant. This article summarizes the present understanding of AD progression and gathers biochemical evidence from various works on natural products that can be useful in the management of this disease.

Studies on the mechanism of acute inhibition of thyroglobulin hydrolysis by iodine

1985 ◽  
Vol 108 (4) ◽  
pp. 511-517 ◽  
Author(s):  
Nandalal Bagchi ◽  
Birdie Shivers ◽  
Thomas R. Brown
Keyword(s):  
Time Course ◽  
Period 2 ◽  
Iodotyrosine Deiodinase ◽  
Rate Of Hydrolysis ◽  
Underlying Mechanisms ◽  
Excess Iodide ◽  
Sites Of Action ◽  
Hydrolysis Of

Abstract. Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of Nal to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4C1 and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis. Our data are consistent with the hypothesis that excess iodide acutely inhibits thyroglobulin hydrolysis by increasing the resistance of thyroglobulin to proteolytic degradation through increased iodination and coupling.

scholarly journals Perspective: Nonreproductive Sites of Action of Reproductive Hormones*

Endocrinology ◽  
2001 ◽  
Vol 142 (6) ◽  
pp. 2200-2204 ◽  
Author(s):  
S. C. Manolagas ◽  
S. Kousteni
Keyword(s):  
Reproductive Hormones ◽  
Sites Of Action

Ion channels and G protein-coupled receptors as targets for invertebrate pest control: from past challenges to practical insecticides

2021 ◽  
Author(s):  
Yoshihisa Ozoe
Keyword(s):  
Ion Channels ◽  
G Protein ◽  
Pest Control ◽  
Gaba Receptors ◽  
Chloride Channels ◽  
Structural Changes ◽  
G Protein Coupled Receptors ◽  
Octopamine Receptors ◽  
Sites Of Action ◽  
G Protein Coupled

Abstract In the late 1970s, we discovered that toxic bicyclic phosphates inhibit the generation of miniature inhibitory junction potentials, implying their antagonism of γ-aminobutyric acid (GABA) receptors (GABARs; GABA-gated chloride channels). This unique mode of action provided a strong incentive for our research on GABARs in later years. Furthermore, minor structural changes conferred insect GABAR selectivity to this class of compounds, convincing us of the possibility of GABARs as targets for insecticides. Forty years later, third-generation insecticides acting as allosteric modulator antagonists at a distinctive site of action in insect GABARs were developed. G protein-coupled receptors (GPCRs) are also promising targets for pest control. We characterized phenolamine receptors functionally and pharmacologically. Of the tested receptors, β-adrenergic-like octopamine receptors were revealed to be the most sensitive to the acaricide/insecticide amitraz. Given the presence of multiple sites of action, ion channels and GPCRs remain potential targets for invertebrate pest control.

Diverse identities and sites of action of cochlear neurotransmitters

2021 ◽  
pp. 108278
Author(s):  
Siân R. Kitcher ◽  
Alia M. Pederson ◽  
Catherine J.C. Weisz
Keyword(s):  
Sites Of Action

Volatile Anesthetics Affect Nutrient Availability in Yeast

Genetics ◽  
2002 ◽  
Vol 161 (2) ◽  
pp. 563-574
Author(s):  
Laura K Palmer ◽  
Darren Wolfe ◽  
Jessica L Keeley ◽  
Ralph L Keil
Keyword(s):  
Amino Acids ◽  
Nutrient Availability ◽  
Wild Type Strain ◽  
Volatile Anesthetic ◽  
Volatile Anesthetics ◽  
Wild Type ◽  
Anesthetic Exposure ◽  
Sites Of Action ◽  
Insight Into ◽  
Lines Of Evidence

Abstract Volatile anesthetics affect all cells and tissues tested, but their mechanisms and sites of action remain unknown. To gain insight into the cellular activities of anesthetics, we have isolated genes that, when overexpressed, render Saccharomyces cerevisiae resistant to the volatile anesthetic isoflurane. One of these genes, WAK3/TAT1, encodes a permease that transports amino acids including leucine and tryptophan, for which our wild-type strain is auxotrophic. This suggests that availability of amino acids may play a key role in anesthetic response. Multiple lines of evidence support this proposal: (i) Deletion or overexpression of permeases that transport leucine and/or tryptophan alters anesthetic response; (ii) prototrophic strains are anesthetic resistant; (iii) altered concentrations of leucine and tryptophan in the medium affect anesthetic response; and (iv) uptake of leucine and tryptophan is inhibited during anesthetic exposure. Not all amino acids are critical for this response since we find that overexpression of the lysine permease does not affect anesthetic sensitivity. These findings are consistent with models in which anesthetics have a physiologically important effect on availability of specific amino acids by altering function of their permeases. In addition, we show that there is a relationship between nutrient availability and ubiquitin metabolism in this response.

scholarly journals Petasin and isopetasin reduce CGRP release from trigeminal afferents indicating an inhibitory effect on TRPA1 and TRPV1 receptor channels

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Johanna Kleeberg-Hartmann ◽  
Birgit Vogler ◽  
Karl Messlinger
Keyword(s):  
Inhibitory Effect ◽  
Transient Receptor Potential Channels ◽  
Mustard Oil ◽  
Root Extract ◽  
Dependent Manner ◽  
Trpv1 Receptor ◽  
Cgrp Release ◽  
Ganglion Neurons ◽  
Sites Of Action ◽  
The Impact

Abstract Background Butterbur root extract with its active ingredients petasin and isopetasin has been used in the prophylactic treatment of migraine for years, while its sites of action are not completely clear. Calcitonin gene-related peptide (CGRP) is known as a biomarker and promoting factor of migraine. We set out to investigate the impact of petasins on the CGRP release from trigeminal afferents induced by activation of the calcium conducting transient receptor potential channels (TRPs) of the subtypes TRPA1 and TRPV1. Methods We used well-established in vitro preparations, the hemisected rodent skull and dissected trigeminal ganglia, to examine the CGRP release from rat and mouse cranial dura mater and trigeminal ganglion neurons, respectively, after pre-incubation with petasin and isopetasin. Mustard oil and capsaicin were used to stimulate TRPA1 and TRPV1 receptor channels. CGRP concentrations were measured with a CGRP enzyme immunoassay. Results Pre-incubation with either petasin or isopetasin reduced mustard oil- and capsaicin-evoked CGRP release compared to vehicle in an approximately dose-dependent manner. These results were validated by additional experiments with mice expressing functionally deleted TRPA1 or TRPV1 receptor channels. Conclusions Earlier findings of TRPA1 receptor channels being involved in the site of action of petasin and isopetasin are confirmed. Furthermore, we suggest an important inhibitory effect on TRPV1 receptor channels and assume a cooperative action between the two TRP receptors. These mechanisms may contribute to the migraine prophylactic effect of petasins.

scholarly journals Weeds Hosting the Soybean Cyst Nematode (Heterodera glycines Ichinohe): Management Implications in Agroecological Systems

Agronomy ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 146
Author(s):  
Leonardo F. Rocha ◽  
Karla L. Gage ◽  
Mirian F. Pimentel ◽  
Jason P. Bond ◽  
Ahmad M. Fakhoury
Keyword(s):  
Weed Management ◽  
Soybean Cyst Nematode ◽  
Heterodera Glycines ◽  
Integrated Management ◽  
Cropping System ◽  
Cyst Nematode ◽  
Weed Species ◽  
Initial Inoculum ◽  
Herbicide Resistant ◽  
Sites Of Action

The soybean cyst nematode (SCN; Heterodera glycines Ichinohe) is a major soybean-yield-limiting soil-borne pathogen, especially in the Midwestern US. Weed management is recommended for SCN integrated management, since some weed species have been reported to be hosts for SCN. The increase in the occurrence of resistance to herbicides complicates weed management and may further direct ecological–evolutionary (eco–evo) feedbacks in plant–pathogen complexes, including interactions between host plants and SCN. In this review, we summarize weed species reported to be hosts of SCN in the US and outline potential weed–SCN management interactions. Plants from 23 families have been reported to host SCN, with Fabaceae including most host species. Out of 116 weeds hosts, 14 species have known herbicide-resistant biotypes to 8 herbicide sites of action. Factors influencing the ability of weeds to host SCN are environmental and edaphic conditions, SCN initial inoculum, weed population levels, and variations in susceptibility of weed biotypes to SCN within a population. The association of SCN on weeds with relatively little fitness cost incurred by the latter may decrease the competitive ability of the crop and increase weed reproduction when SCN is present, feeding back into the probability of selecting for herbicide-resistant weed biotypes. Therefore, proper management of weed hosts of SCN should be a focus of integrated pest management (IPM) strategies to prevent further eco–evo feedbacks in the cropping system.

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