In vitro screen of inhibitors of rat brain serotonin synthesis

1969 ◽  
Vol 47 (5) ◽  
pp. 501-506 ◽  
Author(s):  
E. G. McGeer ◽  
D. A. V. Peters
Keyword(s):  
Rat Brain ◽  
Tryptophan Hydroxylase ◽  
Inhibitory Effect ◽  
Complexing Agents ◽  
Serotonin Synthesis ◽  
Structural Requirements ◽  
Class A ◽  
Numerous Data ◽  
Comparison Of The Results

Over 700 compounds were screened at 10−4 M concentration as inhibitors of the conversion of L-tryptophan-14C to serotonin-14C in crude rat brain homogenates. Most of the compounds had little or no inhibitory effect. Those with strong inhibitory properties were tested as inhibitors of 5-hydroxytryptophan decarboxylase and, if active on the decarboxylase, were assayed as tryptophan hydroxylase inhibitors. Except for a few oxidizing and complexing agents and for some substituted p-phenylenediamines, the compounds found to inhibit tryptophan hydroxylase by >50% belonged to the three types of inhibitors already known, i.e. catechols, phenylalanine and ring-substituted phenylalanines, and 6-substituted tryptophans. The numerous data in this screen make possible some comments as to the structural requirements for activity within each class. A comparison of the results on tryptophan hydroxylase with data on tyrosine hydroxylase inhibition in similar homogenates makes it clear that two separate, if somewhat similar, enzymes are involved.

IN VITRO SCREEN OF INHIBITORS OF RAT BRAIN TYROSINE HYDROXYLASE

1967 ◽  
Vol 45 (1) ◽  
pp. 115-131 ◽  
Author(s):  
E. G. McGeer ◽  
P. L. McGeer
Keyword(s):  
Tyrosine Hydroxylase ◽  
Rat Brain ◽  
Inhibitory Activity ◽  
Brain Homogenate ◽  
Inhibitory Effect ◽  
Side Chain ◽  
Complexing Agents ◽  
Hydroxy Groups ◽  
Brain Tyrosine Hydroxylase

Over 600 compounds were tested at 10−4 M concentration as inhibitors of tyrosine hydroxylase activity in crude rat-brain homogenate. Most of the compounds had little or no inhibitory effect and those with strong inhibitory properties were, except for a very few oxidizing and complexing agents, all close structural analogues of tyrosine or of its catechol metabolites. Data obtained in this screen are generally in accord with previous data reported in the literature. For high inhibitory activity in the tyrosine series, side-chain substitution is critical. N-Substitution is particularly undesirable. For high inhibitory activity in the catechol series, the ring hydroxy groups should be 3,4 in relation to a C—C—N side chain. Further ring substitution is undesirable, but some side-chain substitution is permissible.

Inhibitory effect of somatostatin on vagal motoneurons in the rat brain stem in vitro

1989 ◽  
Vol 256 (1) ◽  
pp. C155-C159 ◽  
Author(s):  
J. Nabekura ◽  
Y. Mizuno ◽  
Y. Oomura
Keyword(s):  
Brain Stem ◽  
Rat Brain ◽  
Reversal Potential ◽  
Input Resistance ◽  
Inhibitory Effect ◽  
Hill Coefficient ◽  
Resting Membrane Potential ◽  
Motor Nucleus ◽  
Dorsal Motor Nucleus

Effects of somatostatin-14 (SRIF) on membrane electrical properties were studied in rat brain stem slice preparations maintained in vitro. SRIF hyperpolarized the resting membrane potential and decreased the input resistance of more than two-thirds of the 85 vagal motoneurons tested in the dorsal motor nucleus of the vagus. These effects persisted under synaptic blockade caused by perfusion with a solution containing tetrodotoxin or a Ca2+-free/high-Mg2+ solution and were dependent on the extracellular SRIF concentration (5 X 10(-8) to 1 X 10(-8) M). The Hill coefficient was estimated to be 2. The reversal potential of SRIF-induced hyperpolarization was affected by changing external K+ concentration. The results suggest that, in addition to its well-known peripheral action, SRIF may inhibit secretomotor functions of visceral organs by reducing vagal output in the central nervous system.

scholarly journals The biosynthesis of sulphogalactosyldiacylglycerol of rat brain in vitro

1977 ◽  
Vol 166 (3) ◽  
pp. 429-435 ◽  
Author(s):  
G. Subba Rao ◽  
Leonard N. Norcia ◽  
Joanne Pieringer ◽  
Ronald A. Pieringer
Keyword(s):  
Enzyme Activity ◽  
Rat Brain ◽  
Enzyme Preparation ◽  
Microsomal Fraction ◽  
Inhibitory Effect ◽  
Subcellular Fractions ◽  
Triton X ◽  
Derivatives Of

Triton X-100 extracts of rat brain microsomal fraction catalyse the formation of sulphogalactosyldiacylglycerol from galactosyldiacylglycerol and adenosine 3′-phosphate 5′-sulphatophosphate. Of the various subcellular fractions of brain assayed, the microsomal fraction contained most (79%) of the adenosine 3′-phosphate 5′-sulphatophosphate–galactosyldiacylglycerol sulphotransferase activity. The enzyme activity was stimulated by Triton X-100 and showed linearity with increasing time, concentrations of enzyme and added substrates. ATP and KF prolonged the linearity of the activity with time, but ATP had an overall inhibitory effect on the sulphotransferase. Both ATP and KF inhibit the degradation of adenosine 3′-phosphate 5′-sulphatophosphate, which probably causes the increased linearity of the sulphotransferase reaction with time. The enzyme preparation did not catalyse the transfer of sulphate from adenosine 3′-phosphate 5′-sulphatophosphate to either cholesterol or galabiosyldiacylglycerol (galactosylgalactosyldiacylglycerol). Significant differences between the formation of sulphogalactosyldiacylglycerol and cerebroside sulphate catalysed by the same enzyme preparation were noted. ATP and Mg2+ strongly inhibit the formation of sulphogalactosyldiacylglycerol but equally strongly stimulate the synthesis of cerebroside sulphate. The apparent Km for galactosyldiacylglycerol is 200μm, and that for cerebroside is 45μm. Galactosyldiacylglycerol and cerebroside are mutually inhibitory toward the synthesis of sulphated derivatives of each. These data do not necessarily lead to the conclusion that two sulphotransferases are present, but they do indicate a possible means of controlling the synthesis of these two sulpholipids.

α1-Adrenergic receptor involvement in norepinephrine–ethanol inhibition of rat brain Na+-K+ ATPase and in ethanol tolerance

1985 ◽  
Vol 63 (9) ◽  
pp. 1075-1079 ◽  
Author(s):  
N. Rangaraj ◽  
H. Kalant ◽  
F. Beaugé
Keyword(s):  
Rat Brain ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Receptor Antagonists ◽  
Concentration Dependent Manner ◽  
Brain Membrane ◽  
Hypothermic Effect ◽  
Wb 4101 ◽  
Number Of Binding Sites

Norepinephrine (NE) sensitization of rat brain Na+–K+ ATPase to ethanol (EtOH) inhibition appears to be mediated by α1-adrenoreceptors, since it was reversed by prazosin and WB-4101 (α1-receptor antagonists) in a concentration-dependent manner, but not by yohimbine and piperoxan (α2-receptor antagonists). In addition, clonidine (α2-agonist) and methoxamine (central receptor type uncertain) produced very little sensitization. Chronic EtOH administration to rats for 3 weeks produced tolerance to the hypothermic effect of test doses of EtOH (3 g/kg, i.p.) and a decreased inhibitory effect of NE + EtOH on the enzyme in vitro. This inhibition was still prevented by prazosin and WB-4101. However, the binding of tritiated WB-4101 and prazosin to brain membrane preparations from control and EtOH-tolerant rats revealed that the maximum number of binding sites (Bmax) and the dissociation constant (KD) of α1-adrenoreceptors were decreased after tolerance development. These changes in numbers and binding properties of α1-adrenoreceptors probably account for the decreased NE sensitization of the ATPase to EtOH inhibition in preparations from EtOH-tolerant rats.

Kinetics of inhibition of acetylcholinesterase by 9-hydrazino-1,2,3,4-tetrahydroacridine and 9-amino-10-methyl-1,2,3,4-tetrahydroacridinium in vitro

1980 ◽  
Vol 45 (3) ◽  
pp. 966-976 ◽  
Author(s):  
Jiří Patočka ◽  
Jiří Bajgar ◽  
Jiří Bielavský
Keyword(s):  
Rat Brain ◽  
Active Center ◽  
Active Surface ◽  
Competitive Inhibitor ◽  
Inhibitory Effect ◽  
Inhibitor Molecule ◽  
Hydrophobic Domain ◽  
Noncompetitive Inhibitor ◽  
Brain Acetylcholinesterase

The kinetics was studied of the inhibition of solubilized rat brain acetylcholinesterase by 9-hydrazino-1,2,3,4-terahydroacridine (THH) and 9-amino-10-methyl-1,2,3,4-tetrahydroacridinium (QTHA); the inhibitory effect was compared with the effect of tacrine (9-amino-1,2,3,4-tetrahydroacridine, THA). It was observed that THH is a reversible, noncompetitive inhibitor of rat brain acetylcholinesterase (Ki = 0.16 μM) and that it binds, similarly to THA, to the hydrophobic domain of the active center of acetylcholinesterase thus simultaneously inhibiting the formation of complex ES2 with acetylcholine as substrate. This eliminates the inhibition of acetylcholinesterase by an excess of substrate. QTHA is a mixed, competitive-non-competitive inhibitor characterized by KI comp = 5.3 μM and Ki noncomp = 0.08 μM. QTHA binds to an entirely different site of the active surface of acetylcholinesterase than THA and THH. This binding site is most likely the so-called β-anionic or also peripheric anionic site to which, e.g. atropine is also bound. Both inhibitors studied form with acetylcholinesterase a reversible, enzymatically inactive complex in which one inhibitor molecule is bonded to each active center of the enzyme.

Inhibitory effect of prostaglandin A2 on Na+-K+ -ATPase activity in synaptic plasma membrane of rat brain in vitro

1982 ◽  
Vol 14 (5) ◽  
pp. 347-350 ◽  
Author(s):  
Yasuko Shibata ◽  
Hidemaro Ohzeki ◽  
Masanori Sato ◽  
Yasuhiko Suzuki ◽  
Hisashi Takiguchi
Keyword(s):  
Plasma Membrane ◽  
Atpase Activity ◽  
Rat Brain ◽  
Inhibitory Effect ◽  
Synaptic Plasma Membrane ◽  
Prostaglandin A2

scholarly journals Protective role of Limonium bonduelli extract against non-enzymatic peroxidation in brain and testes induced by iron in vitro.

2017 ◽  
Vol 9 (1) ◽  
pp. 72
Author(s):  
Amel Amrani ◽  
Nassima Boubekri ◽  
Ouahiba Benaissa ◽  
Djamila Zama ◽  
Fadila Benayache ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Rat Brain ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Dependent Manner ◽  
Phytochemical Content ◽  
Butanol Extract ◽  
Aerial Parts

<p>Infertility and Neurodegerative diseases have been linked to oxidative stress arising from peroxidation of membrane biomolecules and high levels of iron have been reported to play an important role. The present study sought to determine the antioxidant activity and protective ability of <em>n</em>-butanol extract of <em>Limonium bonduelli</em> on lipid peroxidation induced by FeSO<sub>4</sub> in rat brain and testes homogenates <em>in vitro</em>. <em>n</em>-butanol extract of the aerial parts (leaves and flowers)<em> </em>was prepared, and the ability of the extract to inhibit FeSO<sub>4</sub> induced lipid peroxidation in isolated rat brain and testes was determined using spectrophotometric method. The study revealed that the extract inhibited malondialdehyde (MDA) production in FeSO<sub>4 </sub>induced lipid peroxidation in the brain and testes in a dose-dependent manner and the highest percentage of the inhibition was 89.80% similar to vitamin C in the same concentration (100 µg/mL) in brain and 82.33% in testes (200 µg/mL). <em>Limonium bonduelli</em> extract<strong> </strong>demonstrated important anti-lipid peroxidative effect, which may be useful in preventing the progress of various oxidative stress related diseases. The higher inhibitory effect of the extract could be attributed to its phytochemical content.</p>

Inhibitory effect in vitro of PR toxin, a mycotoxin from Penicillium roqueforti, on the mitochondrial HCO3−-ATPase of the rat brain, heart and kidney

Toxicon ◽  
1986 ◽  
Vol 24 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Kwei-Perng Hsieh ◽  
Sue Yu ◽  
Yau-Huei Wei ◽  
Chieh-Fu Chen ◽  
Ru-Dong Wei
Keyword(s):  
Rat Brain ◽  
Inhibitory Effect ◽  
Penicillium Roqueforti ◽  
Toxin A
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