scholarly journals Modulatory Effects of Regional Cortical Activation on the Onset Responses of the Cat Medial Geniculate Neurons

1997 ◽  
Vol 77 (2) ◽  
pp. 896-908 ◽  
Author(s):  
Jufang He
Keyword(s):  
Sound Intensity ◽  
Noise Burst ◽  
Inhibitory Effect ◽  
Cortical Activation ◽  
Facilitatory Effect ◽  
Stimulation Site ◽  
Inhibitory Effects ◽  
Medial Geniculate ◽  
High Sound ◽  
Onset Responses

He, Jufang. Modulatory effects of regional cortical activation on the onset responses of the cat medial geniculate neurons. J. Neurophysiol. 77: 896–908, 1997. Corticofugal modulation on activity of the medial geniculate body (MGB) was examined by locally activating the primary auditory cortex (AI) and looking for effects on the onset responses of MGB neurons to acoustic stimuli. Of 103 MGB neurons recorded from 13 hemispheres of 11 animals, 91 neurons (88%) showed either a facilitatory or inhibitory effect or both; of these neurons, 72 showed facilitatory effects and 25 inhibitory effects. The average facilitatory effect was large, with a mean increase of 62.4%. Small inhibitory effects (mean: −16.2%) were obtained from a few neurons (6 of 103) when a pure tone stimulus was used, whereas the effect became larger and more frequent when a noise burst stimulus was used (mean: −27.3%, n = 22 of 27 neurons). Activation of an AI site having the same best frequency (BF) as the MGB neuron being recorded from produced mainly a facilitatory effect on MGB neuronal responses to pure tones. Activation of AI at a site neighboring the BF site produced inhibitory effects on the MGB response when noise burst stimuli were used. We found that the effective stimulation sites in AI that could modulate MGB activity formed patchlike maps with a diameter of 1.13 ± 0.09 (SE) mm (range 0.6–1.9 mm, n = 15) being larger than the patches of thalamocortical terminal fields. Examining the effects of sound intensities, of 18 neurons tested 9 neurons showed a larger effect for low-sound-intensity stimuli and small or no effects for high-sound-intensity stimuli. These were named low-sound-intensity effective neurons. Five neurons showed high sound intensity effectiveness and four were non-intensity specific. Most low-sound-intensity effective neurons were monotonic rate-intensity function neurons. The AI cortical modulatory effect was frequency specific, because 15 of 27 neurons showed a larger facilitatory effect when a BF stimulus was used rather than a stimulus of any other frequency. The corticothalamic connection between the recording site in MGB and the most effective stimulation site in AI was confirmed by injecting wheat germ agglutinin–horseradish peroxidase tracer at the stimulation site and producing a small lesion in the recording site. The results suggest that 1) the large facilitation effects obtained by AI activation at the region that directly projected to the MGB could be the result mainly of the direct projection terminals to the MGB relay neurons; 2) the large size patches of the effective stimulation site in AI could be due to widely ramifying corticothalamic projections; and 3) the corticofugal projection selectively gates auditory information mainly by a facilitatory effect, although there is also an inhibitory effect that depends on the sound stimulus used.

Corticofugal Modulation on Both on andoff Responses in the Nonlemniscal Auditory Thalamus of the Guinea Pig

2003 ◽  
Vol 89 (1) ◽  
pp. 367-381 ◽  
Author(s):  
Jufang He
Keyword(s):  
Auditory Cortex ◽  
Inhibitory Effect ◽  
Border Region ◽  
Cortical Activation ◽  
Facilitatory Effect ◽  
Auditory Signal ◽  
Inhibitory Input ◽  
Auditory Information ◽  
Medial Geniculate ◽  
Corticofugal Modulation

Corticofugal modulation on both on andoff responses in various nuclei in the medial geniculate body (MGB) was examined by locally activating the auditory cortex and looking for effects on the neuronal responses to acoustic stimuli. In contrast with a major corticofugal facilitatory effect on theon neurons in the lemniscal nucleus of the MGB of the guinea pigs, of 132 on neurons tested in three conditions with cortical activation through each of three implanted electrodes, the majority of the tested conditions (319/396) that were sampled from the nonlemniscal nuclei of the MGB received inhibitory modulation from the activated cortex. This inhibitory effect was >50% for 99 cases while the auditory cortex was activated. Most of the offand on-off MGB neurons (44/54) showed a facilitatory effect of 111.4 ± 99.9%, and three showed a small inhibitory effect of 25.7 ± 5.8% on their off responses. Thirty neurons in the border region between the lemniscal and nonlemniscal MGB showed mainly facilitatory corticofugal effects on both on andoff responses. Meanwhile, cortical stimulation induced almost exclusive inhibitory effects on the on response and facilitatory effects on the off response in the MGcm. It is suggested that the off response is produced as a disinhibition from the inhibitory input of the auditory stimulus. The present results provide a possible explanation for selective gating of the auditory information through the lemniscal MGB while switching off other unwanted sensory signals and the interference from the limbic system, leaving the other auditory cortex prepared to process only the auditory signal.

Modulatory Effect of Cortical Activation on the Lemniscal Auditory Thalamus of the Guinea Pig

2002 ◽  
Vol 88 (2) ◽  
pp. 1040-1050 ◽  
Author(s):  
Jufang He ◽  
Yan-Qin Yu ◽  
Ying Xiong ◽  
Tsutomu Hashikawa ◽  
Ying-Shing Chan
Keyword(s):  
Guinea Pig ◽  
Auditory Cortex ◽  
Firing Pattern ◽  
Inhibitory Effect ◽  
Electrical Activation ◽  
Facilitatory Effect ◽  
Thalamic Neurons ◽  
Auditory Thalamus ◽  
Medial Geniculate ◽  
Corticofugal Modulation

In the present study, we investigated the point-to-point modulatory effects from the auditory cortex to the thalamus in the guinea pig. Corticofugal modulation on thalamic neurons was studied by electrical activation of the auditory cortex. The modulation effect was sampled along the frontal or sagittal planes of the auditory thalamus, focusing on the ventral division (MGv) of the medial geniculate body (MGB). Electrical activation was targeted at the anterior and dorsocaudal auditory fields, to which the MGv projects and from which it assumptively receives reciprocal projections. Of the 101 MGv neurons examined by activation of the auditory cortex through passing pulse trains of 100–200 μA current into one after another of the three implanted electrodes (101 neurons × 3 stimulation sites = 303 cases), 208 cases showed a facilitatory effect, 85 showed no effect, and only 10 cases (7 neurons) showed an inhibitory effect. Among the cases of facilitation, 63 cases showed a facilitatory effect >100%, and 145 cases showed a facilitatory effect from 20–100%. The corticofugal modulatory effect on the MGv of the guinea pig showed a widespread, strong facilitatory effect and very little inhibitory effect. The MGv neurons showed the greatest facilitations to stimulation by the cortical sites, with the closest correspondence in BF. Six of seven neurons showed an elevation of the rate-frequency functions when the auditory cortex was activated. The comparative results of the corticofugal modulatory effects on the MGv of the guinea pig and the cat, together with anatomical findings, hint that the strong facilitatory effect is generated through the strong corticothalamic direct connection and that the weak inhibitory effect might be mainly generated via the interneurons of the MGv. The temporal firing pattern of neuronal response to auditory stimulus was also modulated by cortical stimulation. The mean first-spike latency increased significantly from 15.7 ± 5.3 ms with only noise-burst stimulus to 18.3 ± 4.9 ms ( n = 5, P < 0.01, paired t-test), while the auditory cortex was activated with a train of 10 pulses. Taking these results together with those of previous experiments conducted on the cat, we speculate that the relatively weaker inhibitory effect compared with that in the cat could be due to the smaller number of interneurons in the guinea pig MGB. The corticofugal modulation of the firing pattern of the thalamic neurons might enable single neurons to encode more auditory information using not only the firing rate but also the firing pattern.

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

Inhibition of ADP-Induced Responses in Human Platelets by Agents Elevating the Cyclic AMP Level: Comparison of Aggregation and Shape Change

1984 ◽  
Vol 52 (03) ◽  
pp. 333-335 ◽  
Author(s):  
Vider M Steen ◽  
Holm Holmsen
Keyword(s):  
Inhibitory Action ◽  
Human Platelet ◽  
Platelet Rich Plasma ◽  
Shape Change ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Inhibitory Effects ◽  
Early Step ◽  
Stimulus Response ◽  
Sequential Relationship

SummaryThe inhibitory effect of cAMP-elevating agents on shape change and aggregation in human platelets was studied to improve the understanding of the sequential relationship between these two responses.Human platelet-rich plasma was preincubated for 2 min at 37° C with prostaglandin E1 or adenosine, agents known to elevate the intracellular level of cAMP. Their inhibitory effects on ADP-induced shape change and aggregation were determined both separately and simultaneously. The dose-inhibition patterns for shape change and aggregation were similar for both PGE1 and adenosine. There was no distinct difference between the inhibitory action of these two inhibitors.These observations suggest that elevation of the intracellular concentration of cAMP interferes with an early step in the stimulus-response coupling that is common for aggregation and shape change.

The Inhibitory Effect of Heparin and Related Glycosaminoglycans on Neutrophil Chemotaxis

1984 ◽  
Vol 52 (02) ◽  
pp. 134-137 ◽  
Author(s):  
Yaacov Matzner ◽  
Gerard Marx ◽  
Ruth Drexler ◽  
Amiram Eldor
Keyword(s):  
Specific Binding ◽  
Anticoagulant Activity ◽  
Neutrophil Migration ◽  
Inhibitory Effect ◽  
Chemotactic Factor ◽  
Human Neutrophils ◽  
Boyden Chamber ◽  
Neutrophil Chemotaxis ◽  
Inhibitory Effects ◽  
Chemotactic Factors

SummaryClinical observations have shown that heparin has antiinflammatory activities. The effect of heparin on neutrophil chemotaxis was evaluated in vitro in the Boyden Chamber. This method enabled differentiation between the direct effects of heparin on neutrophil migration and locomotion, and its effects on chemotactic factors. Heparin inhibited both the random migration and directed locomotion of human neutrophils toward zymosan-activated serum (ZAS) and F-met-leu-phe (FMLP). Inhibition was found to be dependent on the concentrations of the heparin and of the chemotactic factors. No specific binding of heparin to the neutrophils could be demonstrated, and heparin’s inhibitory effects were eliminated by simple washing of the cells. When added directly to the chamber containing chemotactic factor, heparin inhibited the chemotactic activity of ZAS but not that of FMLP, suggesting a direct inhibitory effect against C5a, the principal chemotactic factor in ZAS.Experiments performed with low-molecular-weight heparin, N-desulfated heparin, dextran sulfate, chondroitin sulfate and dextran indicated that the inhibitory effects of heparin on neutrophil chemotaxis are not related to its anticoagulant activity, but probably depend on the degree of sulfation of the heparin molecule.

Inhibition of Yeast Growth by Tryptamine and Recovery with Tryptophan

2020 ◽  
Vol 16 (1) ◽  
pp. 48-52 ◽  
Author(s):  
Chandrika Kadkol ◽  
Ian Macreadie
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Carbon Source ◽  
Competitive Inhibition ◽  
Yeast Species ◽  
Inhibitory Effect ◽  
The Body ◽  
Inhibitory Effects ◽  
Trna Synthetases ◽  
Fermentative Growth ◽  
Biogenic Monoamine

Background: Tryptamine, a biogenic monoamine that is present in trace levels in the mammalian central nervous system, has probable roles as a neurotransmitter and/or a neuromodulator and may be associated with various neuropsychiatric disorders. One of the ways tryptamine may affect the body is by the competitive inhibition of the attachment of tryptophan to tryptophanyl tRNA synthetases. Methods: This study has explored the effects of tryptamine on growth of six yeast species (Saccharomyces cerevisiae, Candida glabrata, C. krusei, C. dubliniensis, C. tropicalis and C. lusitaniae) in media with glucose or ethanol as the carbon source, as well as recovery of growth inhibition by the addition of tryptophan. Results: Tryptamine was found to have an inhibitory effect on respiratory growth of all yeast species when grown with ethanol as the carbon source. Tryptamine also inhibited fermentative growth of Saccharomyces cerevisiae, C. krusei and C. tropicalis with glucose as the carbon source. In most cases the inhibitory effects were reduced by added tryptophan. Conclusion: The results obtained in this study are consistent with tryptamine competing with tryptophan to bind mitochondrial and cytoplasmic tryptophanyl tRNA synthetases in yeast: effects on mitochondrial and cytoplasmic protein synthesis can be studied as a function of growth with glucose or ethanol as a carbon source. Of the yeast species tested, there is variation in the sensitivity to tryptamine and the rescue by tryptophan. The current study suggests appropriate yeast strains and approaches for further studies.

Molecular Mechanisms of the Inhibitory Effects of Bupivacaine, Levobupivacaine, and Ropivacaine on Sarcolemmal Adenosine Triphosphate–sensitive Potassium Channels in the Cardiovascular System

2004 ◽  
Vol 101 (2) ◽  
pp. 390-398 ◽  
Author(s):  
Takashi Kawano ◽  
Shuzo Oshita ◽  
Akira Takahashi ◽  
Yasuo Tsutsumi ◽  
Yoshinobu Tomiyama ◽  
...  
Keyword(s):  
Cardiovascular System ◽  
Adenosine Triphosphate ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
Transmembrane Domain ◽  
Katp Channels ◽  
Inhibitory Effect ◽  
Amino Acid Residues ◽  
Sulfonylurea Receptor ◽  
Inhibitory Effects

Background Sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channels in the cardiovascular system may be involved in bupivacaine-induced cardiovascular toxicity. The authors investigated the effects of local anesthetics on the activity of reconstituted KATP channels encoded by inwardly rectifying potassium channel (Kir6.0) and sulfonylurea receptor (SUR) subunits. Methods The authors used an inside-out patch clamp configuration to investigate the effects of bupivacaine, levobupivacaine, and ropivacaine on the activity of reconstituted KATP channels expressed in COS-7 cells and containing wild-type, mutant, or chimeric SURs. Results Bupivacaine inhibited the activities of cardiac KATP channels (IC50 = 52 microm) stereoselectively (levobupivacaine, IC50 = 168 microm; ropivacaine, IC50 = 249 microm). Local anesthetics also inhibited the activities of channels formed by the truncated isoform of Kir6.2 (Kir6.2 delta C36) stereoselectively. Mutations in the cytosolic end of the second transmembrane domain of Kir6.2 markedly decreased both the local anesthetics' affinity and stereoselectivity. The local anesthetics blocked cardiac KATP channels with approximately eightfold higher potency than vascular KATP channels; the potency depended on the SUR subtype. The 42 amino acid residues at the C-terminal tail of SUR2A, but not SUR1 or SUR2B, enhanced the inhibitory effect of bupivacaine on the Kir6.0 subunit. Conclusions Inhibitory effects of local anesthetics on KATP channels in the cardiovascular system are (1) stereoselective: bupivacaine was more potent than levobupivacaine and ropivacaine; and (2) tissue specific: local anesthetics blocked cardiac KATP channels more potently than vascular KATP channels, via the intracellular pore mouth of the Kir6.0 subunit and the 42 amino acids at the C-terminal tail of the SUR2A subunit, respectively.

scholarly journals Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Vicky Mody ◽  
Joanna Ho ◽  
Savannah Wills ◽  
Ahmed Mawri ◽  
Latasha Lawson ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dynamics Simulation ◽  
Simulation Studies ◽  
Inhibitory Effects ◽  
Major Threat ◽  
Main Protease ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Computational Molecular Modeling

AbstractEmerging outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is a major threat to public health. The morbidity is increasing due to lack of SARS-CoV-2 specific drugs. Herein, we have identified potential drugs that target the 3-chymotrypsin like protease (3CLpro), the main protease that is pivotal for the replication of SARS-CoV-2. Computational molecular modeling was used to screen 3987 FDA approved drugs, and 47 drugs were selected to study their inhibitory effects on SARS-CoV-2 specific 3CLpro enzyme in vitro. Our results indicate that boceprevir, ombitasvir, paritaprevir, tipranavir, ivermectin, and micafungin exhibited inhibitory effect towards 3CLpro enzymatic activity. The 100 ns molecular dynamics simulation studies showed that ivermectin may require homodimeric form of 3CLpro enzyme for its inhibitory activity. In summary, these molecules could be useful to develop highly specific therapeutically viable drugs to inhibit the SARS-CoV-2 replication either alone or in combination with drugs specific for other SARS-CoV-2 viral targets.

scholarly journals Study on the Inhibitory Activity of a Synthetic Defensin Derived from Barley Endosperm against Common Food Spoilage Yeast

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 165
Author(s):  
Laila N. Shwaiki ◽  
Aylin W. Sahin ◽  
Elke K. Arendt
Keyword(s):  
Apple Juice ◽  
Digestive Enzyme ◽  
Inhibitory Effect ◽  
Food Preservation ◽  
Food Spoilage ◽  
Inhibitory Effects ◽  
Barley Endosperm ◽  
Spoilage Yeast ◽  
Spoilage Yeasts ◽  
Spoilage Microorganisms

In the food industry, food spoilage is a real issue that can lead to a significant amount of waste. Although current preservation techniques are being applied to reduce the occurrence of spoilage microorganisms, the problem persists. Food spoilage yeast are part of this dilemma, with common spoilers such as Zygosaccharomyces, Kluyveromyces, Debaryomyces and Saccharomyces frequently encountered. Antimicrobial peptides derived from plants have risen in popularity due to their ability to reduce spoilage. This study examines the potential application of a synthetic defensin peptide derived from barley endosperm. Its inhibitory effect against common spoilage yeasts, its mechanisms of action (membrane permeabilisation and overproduction of reactive oxygen species), and its stability in different conditions were characterised. The safety of the peptide was evaluated through a haemolysis and cytotoxicity assay, and no adverse effects were found. Both assays were performed to understand the effect of the peptide if it were to be consumed. Its ability to be degraded by a digestive enzyme was also examined for its safety. Finally, the peptide was successfully applied to different beverages and maintained the same inhibitory effects in apple juice as was observed in the antiyeast assays, providing further support for its application in food preservation.

scholarly journals Amphetamine-Decreased Progesterone and Estradiol Release in Rat Granulosa Cells: The Regulatory Role of cAMP- and Ca2+-Mediated Signaling Pathways

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 493
Author(s):  
 Chung-Yu Chen ◽  
Chien-Rung Chen ◽  
Chiao-Nan Chen ◽  
Paulus S. Wang ◽  
Toby Mündel ◽  
...  
Keyword(s):  
Granulosa Cells ◽  
Prostaglandin F2α ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Steroidogenic Enzyme ◽  
Estradiol Secretion ◽  
Basal Release ◽  
Ca2 Channels

The purpose of this study is to evaluate the amphetamine effects on progesterone and estradiol production in rat granulosa cells and the underlying cellular regulatory mechanisms. Freshly dispersed rat granulosa cells were cultured with various test drugs in the presence of amphetamine, and the estradiol/progesterone production and the cytosolic cAMP level were measured. Additionally, the cytosolic-free Ca2+ concentrations ([Ca2+]i) were measured to examine the role of Ca2+ influx in the presence of amphetamine. Amphetamine in vitro inhibited both basal and porcine follicle-stimulating hormone-stimulated estradiol/progesterone release, and amphetamine significantly decreased steroidogenic enzyme activities. Adding 8-Bromo-cAMP did not recover the inhibitory effects of amphetamine on progesterone and estradiol release. H89 significantly decreased progesterone and estradiol basal release but failed to enhance a further amphetamine inhibitory effect. Amphetamine was capable of further suppressing the release of estradiol release under the presence of nifedipine. Pretreatment with the amphetamine for 2 h decreased the basal [Ca2+]i and prostaglandin F2α-stimulated increase of [Ca2+]i. Amphetamine inhibits progesterone and estradiol secretion in rat granulosa cells through a mechanism involving decreased PKA-downstream steroidogenic enzyme activity and L-type Ca2+ channels. Our current findings show that it is necessary to study the possibility of amphetamine perturbing reproduction in females.

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