Molecular Mechanism of the Inhibitory Effect of Cobalt Ion on Thermolysin Activity and the Suppressive Effect of Calcium Ion on the Cobalt Ion-dependent Inactivation of Thermolysin

2007 ◽  
Vol 141 (6) ◽  
pp. 879-888 ◽  
Author(s):  
Y. Hashida ◽  
K. Inouye
Keyword(s):  
Molecular Mechanism ◽  
Calcium Ion ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Cobalt Ion ◽  
Dependent Inactivation

Interaction between cortisol and arachidonic acid on the secretion of LH from ovine pituitary tissue

1991 ◽  
Vol 131 (1) ◽  
pp. 87-94 ◽  
Author(s):  
A. W. Nangalama ◽  
G. P. Moberg
Keyword(s):  
Arachidonic Acid ◽  
Plasma Membrane ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Adrenal Steroids ◽  
Membrane Phospholipids ◽  
Pituitary Tissue ◽  
Receptor Sites ◽  
Lh Release ◽  
Gonadotrophin Releasing Hormone

ABSTRACT In several species, glucocorticoids act directly on the pituitary gonadotroph to suppress the gonadotrophin-releasing hormone (GnRH)-induced secretion of the gonadotrophins, especially LH. A mechanism for this action of these adrenal steroids has not been established, but it appears that the glucocorticoids influence LH release by acting on one or more post-receptor sites. This study investigated whether glucocorticoids disrupt GnRH-induced LH release by altering the liberation of arachidonic acid from plasma membrane phospholipids, a component of GnRH-induced LH release. Using perifused ovine pituitary tissue, it was established that exposure of gonadotrophs to 1–1000 nmol cortisol/l for 4 h or longer significantly reduced GnRH-stimulated LH release with the maximal inhibitory effect being observed after 6 h of exposure to cortisol. This suppressive effect of cortisol could be reversed by administration of arachidonic acid, which in its own right could stimulate LH release from ovine pituitary tissue. Furthermore, the inhibitory effect of cortisol on GnRH-stimulated LH release could be directly correlated with decreased pituitary responsiveness to GnRH-stimulated arachidonic acid liberation, consistent with our hypothesis that glucocorticoids can suppress GnRH-induced secretion of LH by reducing the amount of arachidonic acid available for the exocytotic response of GnRH. Journal of Endocrinology (1991) 131, 87–94

scholarly journals An ontogenic study of receptor mechanisms by which acute administration of low-doses of methamphetamine suppresses DOI-induced 5-HT2A-receptor mediated head-twitch response in mice

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yina Sun ◽  
Seetha Chebolu ◽  
Denise Henry ◽  
Sandeep Lankireddy ◽  
Nissar A. Darmani
Keyword(s):  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Acute Administration ◽  
Low Doses ◽  
Head Twitch ◽  
Twitch Response ◽  
Way 100635 ◽  
Direct Acting ◽  
Head Twitch Response ◽  
Stimulation Of

Abstract Background Methamphetamine (MA) is a non-selective monoamine releaser and thus releases serotonin (5-HT), norepinephrine (NE) and dopamine (DA) from corresponding nerve terminals into synapses. DOI ((±)-2, 5-dimethoxy-4-iodoamphetamine) is a direct-acting serotonergic 5-HT2A/C receptor agonist and induces the head-twitch response (HTR) via stimulation of 5-HT2A receptor in mice. While more selective serotonin releasers such as d-fenfluramine evoke the HTR, monoamine reuptake blockers (e.g., cocaine) suppress the DOI-evoked HTR via indirect stimulation of serotonergic 5-HT1A- and adrenergic ɑ2-receptors. Since the induction of HTR by DOI is age-dependent, we investigated whether: (1) during development MA can evoke the HTR by itself, and (2) acute pretreatment with either the selective 5-HT2A receptor antagonist EMD 281014 or low-doses of MA can: (i) modulate the DOI-induced HTR in mice across postnatal days 20, 30 and 60, and (ii) alter the DOI-induced c-fos expression in mice prefrontal cortex (PFC). To further explore the possible modulatory effect of MA on DOI-induced HTR, we investigated whether blockade of inhibitory serotonergic 5-HT1A- or adrenergic ɑ2-receptors by corresponding selective antagonists (WAY 100635 or RS 79948, respectively), can prevent the effect of MA on DOI-induced HTR during aging. Results Although neither EMD 281014 nor MA by themselves could evoke the HTR, acute pretreatment with either EMD 281014 (0.01, 0.05 and 0.1 mg/kg, i.p.) or MA (1, 2.5, 5 mg/kg, i.p.), dose-dependently suppressed the DOI-induced HTR across ages. While WAY 100635 significantly reversed the inhibitory effect of MA in 20- and 30-day old mice, RS 79948 failed to significantly counter MA’s inhibitory effect. Moreover, DOI significantly increased c-fos expressions in several PFC regions. EMD 281014 prevented the DOI-induced increases in c-fos expression. Despite the inhibitory effect of MA on DOI-induced HTR, MA alone or in combination with DOI, significantly increased c-fos expression in several regions of the PFC. Conclusion The suppressive effect of MA on the DOI-evoked HTR appears to be mainly due to functional interactions between the HTR-inducing 5-HT2A receptor and the inhibitory 5-HT1A receptor. The MA-induced increase in c-fos expression in different PFC regions may be due to MA-evoked increases in synaptic concentrations of 5-HT, NE and/or DA.

Urea inhibits hypertonicity-inducible TonEBP expression and action

2001 ◽  
Vol 280 (5) ◽  
pp. F904-F912 ◽  
Author(s):  
Wei Tian ◽  
David M. Cohen
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanism ◽  
Reporter Gene ◽  
Gene Transcription ◽  
Phorbol Ester ◽  
Renal Medulla ◽  
Inhibitory Effect ◽  
Characteristic Set ◽  
Enhancer Element ◽  
Enhancer Binding Protein

Tonicity-responsive genes are regulated by the TonE enhancer element and the tonicity-responsive enhancer binding protein (TonEBP) transcription factor with which it interacts. Urea, a permeant solute coexistent with hypertonic NaCl in the mammalian renal medulla, activates a characteristic set of signaling events that may serve to counteract the effects of NaCl in some contexts. Urea inhibited the ability of hypertonic stressors to increase expression of TonEBP mRNA and also inhibited tonicity-inducible TonE-dependent reporter gene activity. The permeant solute glycerol failed to reproduce these effects, as did cell activators including peptide mitogens and phorbol ester. The inhibitory effect of urea was evident as late as 2 h after the application of hypertonicity. Pharmacological inhibitors of known urea-inducible signaling pathways failed to abolish the inhibitory effect of urea. TonEBP action is incompletely understood, but evidence supports a role for proteasome function and p38 action in regulation; urea failed to inhibit proteasome function or p38 signaling in response to hypertonicity. Consistent with its effect on TonEBP expression and action, urea pretreatment inhibited the effect of hypertonicity on expression of the physiological effector gene, aldose reductase. Taken together, these data 1) define a molecular mechanism of urea-mediated inhibition of tonicity-dependent signaling, and 2) underscore a role for TonEBP abundance in regulating TonE-mediated gene transcription.

The molecular mechanism of fullerene-inhibited aggregation of Alzheimer's β-amyloid peptide fragment

Nanoscale ◽  
2014 ◽  
Vol 6 (16) ◽  
pp. 9752-9762 ◽  
Author(s):  
Luogang Xie ◽  
Yin Luo ◽  
Dongdong Lin ◽  
Wenhui Xi ◽  
Xinju Yang ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Inhibitory Effect ◽  
Amyloid Peptide ◽  
Peptide Fragment ◽  
Experiment Study ◽  
Simulation And Experiment ◽  
Β Amyloid ◽  
Combined Simulation ◽  
Β Amyloid Peptide ◽  
Β Sheet

A combined simulation and experiment study demonstrates that fullerenes inhibit the β-sheet formation of Aβ(16–22) and fullerene hexagonal rings play a significant role on the inhibitory effect.

Growth Inhibition of Granulocyte-Macrophage Colony-Forming Cells by Human Cytidine Deaminase Requires the Catalytic Function of the Protein

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4127-4135 ◽  
Author(s):  
Christine Gran ◽  
Arne Bøyum ◽  
Rune F. Johansen ◽  
Dagfinn Løvhaug ◽  
Erling C. Seeberg
Keyword(s):  
Growth Inhibition ◽  
Specific Activity ◽  
Cytidine Deaminase ◽  
Growth Inhibitor ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Catalytic Function ◽  
Km Value ◽  
Regulatory Potential ◽  
Macrophage Colony

Abstract Previous studies have indicated that cytidine deaminase (CDD) is a potent growth inhibitor of granulocyte-macrophage colony-forming cells (GM-CFC). In this study, we have undertaken molecular cloning and purification of recombinant human CDD to elucidate the growth regulatory potential and mechanism behind the growth suppressive effect. The purified protein had a specific activity of 1.35 × 105 U/mg and a Km value of 30 μmol/L. In the GM-CFC assay, the recombinant protein was shown to reduce colony formation to 50% at 16 pmol/L concentration. Similarly, as was observed with CDD derived from granulocyte extract, the effect depended on the presence of thymidine (≥ 4 × 10-5 mol/L). These results imply that CDD is an extremely potent inhibitor of GM-CFC and that no additional factor from the granulocyte extract is required for the growth inhibitory effect. Modification of CDD by truncation from the C-terminal end, or by amino acid substitution of an active site glutamate residue, eliminated both the enzyme activity and the growth regulatory potential of CDD. Furthermore, CDD fromEscherichia coli was found to be even more effective than human CDD in growth suppression of GM-CFC, with 10-fold higher inhibitory activity corresponding to a 10-fold higher enzymatic activity. Taken together, these results show that the catalytic nucleoside deaminating function of the protein is essential for the growth suppressive effect of CDD. Most probably, CDD exerts growth inhibition by depleting the cytidine and deoxycytidine pool required for DNA synthesis, as addition of deoxycytidine monophosphate, which is not a substrate for CDD, neutralizes the inhibiting effect.

scholarly journals Effect of recombinant interferons alpha and gamma on human bone marrow- derived megakaryocytic progenitor cells

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1173-1179 ◽  
Author(s):  
A Ganser ◽  
C Carlo-Stella ◽  
J Greher ◽  
B Volkers ◽  
D Hoelzer
Keyword(s):  
Bone Marrow ◽  
T Lymphocytes ◽  
Progenitor Cells ◽  
Inhibitory Activity ◽  
Bone Marrow Cells ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Hematopoietic Progenitor Cells ◽  
Adherent Cells ◽  
Hematopoietic Progenitor

Abstract Interferons (IFNs) have been shown to suppress the proliferation of human pluripotent hematopoietic progenitor cells, CFU-GEMM, and committed erythroid (BFU-E, CFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. However, no information is yet available concerning the effect of IFNs on human megakaryocytic progenitor cells CFU-Mk. Furthermore the mechanisms underlying the inhibitory activity of IFNs are still controversial. Therefore highly purified recombinant IFN preparations, rIFN-alpha and rIFN-gamma, were assessed for their influence on in vitro growth of human bone marrow-derived CFU-Mk as well as CFU-GEMM. In addition, the role of hematopoietic accessory cells, that is, adherent cells and T lymphocytes, in the mediation of the suppressive effect of rIFNs was examined. When added to unseparated bone marrow cells, both rIFN preparations significantly inhibited colony formation with 50% inhibition of CFU-Mk occurring at 22 U/mL for rIFN-alpha and 59 U/mL for rIFN-gamma, while 50% inhibition of CFU-GEMM occurred at 59 U/mL for rIFN-alpha and 101 U/mL for rIFN-gamma. The suppressive effect of rIFN-alpha and rIFN-gamma was selectively abolished by monoclonal antibodies (MoAbs) against rIFN-alpha and rIFN- gamma, thus confirming that the inhibitory activity was due to the rIFN preparations used. The antiproliferative effect of rIFN-alpha and rIFN- gamma on CFU-GEMM growth was not associated with a decrease in the percentage of mixed colonies containing megakaryocytic cells as assessed by use of the MoAb C17.28 against platelet glycoprotein IIIa. Removal of adherent cells and T lymphocytes from the target bone marrow cells had no influence on the suppressive effect of rIFN-alpha, whereas it significantly reduced the inhibitory effect of rIFN-gamma on the growth of megakaryocytic colonies and the other hematopoietic progenitors. The data indicate that (1) human megakaryocytopoiesis is markedly inhibited by rIFN-alpha and rIFN-gamma, and (2) the inhibitory effect of rIFN-alpha is due to a direct action on hematopoietic progenitor cells, whereas the effect of rIFN-gamma is mediated to a significant degree through accessory cell populations.

scholarly journals Endogenous Dopamine Suppresses Initiation of Swimming in Prefeeding Zebrafish Larvae

2008 ◽  
Vol 100 (3) ◽  
pp. 1635-1648 ◽  
Author(s):  
Vatsala Thirumalai ◽  
Hollis T. Cline
Keyword(s):  
D2 Receptor ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Resting Membrane Potential ◽  
Downstream Target ◽  
Zebrafish Larvae ◽  
Endogenous Dopamine ◽  
Dopamine Reuptake ◽  
Episode Frequency ◽  
The Brain

Dopamine is a key neuromodulator of locomotory circuits, yet the role that dopamine plays during development of these circuits is less well understood. Here, we describe a suppressive effect of dopamine on swim circuits in larval zebrafish. Zebrafish larvae exhibit marked changes in swimming behavior between 3 days postfertilization (dpf) and 5dpf. We found that swim episodes were fewer and of longer durations at 3 than at 5dpf. At 3dpf, application of dopamine as well as bupropion, a dopamine reuptake blocker, abolished spontaneous fictive swim episodes. Blocking D2 receptors increased frequency of occurrence of episodes and activation of adenylyl cyclase, a downstream target inhibited by D2-receptor signaling, blocked the inhibitory effect of dopamine. Dopamine had no effect on motor neuron firing properties, input impedance, resting membrane potential, or the amplitude of spike afterhyperpolarization. Application of dopamine either to the isolated spinal cord or locally within the cord does not decrease episode frequency, whereas dopamine application to the brain silences episodes, suggesting a supraspinal locus of dopaminergic action. Treating larvae with 10 μM MPTP reduced catecholaminergic innervation in the brain and increased episode frequency. These data indicate that dopamine inhibits the initiation of fictive swimming episodes at 3dpf. We found that at 5dpf, exogenously applied dopamine inhibits swim episodes, yet the dopamine reuptake blocker or the D2-receptor antagonist have no effect on episode frequency. These results led us to propose that endogenous dopamine release transiently suppresses swim circuits in developing zebrafish.

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