Disease relevance of Hemicholinium

• Spontaneous firing of single ganglion cells was observed at all times following hemicholinium-3 injection [1].
• Accumulation of FCH and FDG were comparable in cultured prostate cancer cells, whereas only FCH was inhibited (90%) by hemicholinium-3, a specific inhibitor of choline transport and phosphorylation [2].
• The synthesis of several derivatives based on structural modifications of hemicholinium-3 (HC-3) is not accompanied by potentiation of the neurological toxicity of HC-3 [3].
• Effect of corticosteroids on sciatic nerve-tibialis anterior muscle of rats treated with hemicholinium-3. An experimental approach to a possible mechanism of action of corticosteroids in myasthenia gravis [4].
• Action of hemicholinium-3 on phospholipid metabolism in Krebs II ascites cells [5].

Psychiatry related information on Hemicholinium

• The effects of hemicholinium-3 (HC-3) on spatial discrimination learning were studied [6].
• Amnesia produced by intracerebroventricular injections of hemicholinium-3 in mice was prevented by pretreatment with piracetam-like compounds [7].
• Microgram injections of muscarinic antagonists, atropine or scopolamine, or a choline uptake blocker, hemicholinium-3, elevated frequency thresholds for both self-stimulation sites in a dose-dependent and time-dependent fashion [8].
• The pressor responses to bicuculline methiodide in animals pretreated with the hemicholinium-3 were higher than those seen in saline-pretreated groups, but locomotor activity and heart rate responses to bicuculline methiodide remained unchanged in hemicholinium-3 pretreatment group [9].

High impact information on Hemicholinium

• In the presence of hemicholinium-3, which inhibits Cho transport, the amount of intracellular [14C]Cho metabolites that accumulated during the chase period was higher than in control cells, indicating that PtdCho hydrolysis liberated Cho directly into the cytoplasm [10].
• Vesamicol, an inhibitor of VAChT, and hemicholinium-3, an inhibitor of choline transport, both reduced H82 cell ACh basal release in a dose-dependent manner [11].
• In parallel with the reductions of ACh release, vesamicol and hemicholinium-3 also decreased H82 cell proliferation [11].
• Microinjections within the C1 area of the RVL of scopolamine, the M2-selective muscarinic receptor antagonist AF-DX 116, or the high-affinity choline uptake inhibitor hemicholinium-3 blocked the pressor effects of PHY [12].
• High affinity transport was inhibited by hemicholinium-3 in a competitive manner and was apparently dependent on membrane potential or ion gradients [13].

Chemical compound and disease context of Hemicholinium

• A marked protective action of the corticosteroids prednisolone, hydrocortisone, and dexamethasone has been shown on a hypothetical model of myasthenia gravis, using the rat phrenic nerve-diaphragm preparation treated with hemicholinium-3 [14].
• The first, with Km1 = 7 microM and Vm1 = 200 pmol/h per ganglion is sodium dependent, related to acetylcholine synthesis (43%) and has an IC50 with hemicholinium-3 equal to 50 microM [15].
• Tetrahydroaminoacridine (THA: Tacrine) has previously been shown to reverse deficits in spatial discrimination learning induced by hemicholinium-3 (HC-3) [16].
• Intraventricular injection of hemicholinium-3 4 h before testing resulted in a profound impairment of position discrimination learning which could be overcome by the intramuscular administration of low doses of the muscarinic agonists, arecoline or pilocarpine [17].
• Rats were injected with either saline; A-4 (40 mg/kg, i.p.), a bis tertiary amine derivative of hemicholinium-3; or A-5 (50 micrograms/kg, i.p.), a bis quaternary amine derivative of hemicholinium-3, 1 h prior to moderate fluid percussion brain injury [18].

Biological context of Hemicholinium

• In the absence of extracellular Ca2+ or presence of high Mg2+ levels, the choline mustard did not prevent the appearance of extra striatal hemicholinium-3 binding sites [19].
• Choline uptake is inhibited by hemicholinium-3, but only at high concentrations of the drug (IC50 = 30-80 microM) [20].
• Synthesis of brain ACh was inhibited by chronic infusion of hemicholinium-3 (HC-3) into the cerebral ventricles, and systolic blood pressure was monitored by tail cuff occlusion [21].
• 2. Hemicholinium-3, which blocks ACh synthesis, reduced the amplitude of all synaptic potentials including slow m.e.p.p.s, but only if the nerve was stimulated [22].
• 4. However, deesterification of 2 with subsequent cyclization to the hemiacetal form of hemicholinium-3 (HC-3, 1) is prevented at pH 7.4, possibly by an irreversible binding of 2 to the enzyme [23].

Anatomical context of Hemicholinium

• Indices of cholinergic synaptic function (choline acetyltransferase, hemicholinium-3 binding) indicated substantial hyperactivity in males, especially in the hippocampus, effectively eliminating the normal sex differences for these parameters [24].
• The KD for specific [3H]hemicholinium-3 binding was found to be 31 +/- 4 nM and the Bmax, 5.0 +/- 0.2 pmol/mg protein; a Ki of 16 nM was estimated for hemicholinium-3 as a competitive inhibitor of high-affinity choline transport in electric organ synaptosomes [25].
• In each instance, hemicholinium-3 causes a significant inhibition of control activity at a concentration of 30 microM, a dosage that causes complete photoreceptor outer segment degeneration in mammalian retinas [26].
• This pool of transmitter seemed to be preformed in the synaptic vesicles, rather than synthesized in response to stimuli, as tityustoxin could not release newly synthesized [3H]ACh formed in the presence of vesamicol, and hemicholinium-3 did not prevent the toxin-induced release [27].
• Choline kinase activity in the developing rat spinal cord: differential development of hemicholinium-3 sensitive and insensitive activity [28].

Associations of Hemicholinium with other chemical compounds

• The activity was decreased by hemicholinium-3, an inhibitor of choline uptake and slightly activated by neostigmine, an acetylcholinesterase inhibitor [29].
• 4,4'-Bis-1-hydroxy-2-(4-methylpiperidin-1-yl)ethyl-biphenyl (A-4), a tertiary amine analog of hemicholinium-3 (HC-3), is an inhibitor of the sodium-dependent high-affinity choline uptake (HACU) system [30].
• [3H]Choline uptake by endothelial cells was temperature dependent and was inhibited by the choline analogs hemicholinium-3, deanol, and AF64A [31].
• Pretreatment of the lateral septal area with hemicholinium-3, which depletes stores of acetylcholine, partially blocked the pressor effect of bradykinin but not that of Ach [32].
• Stereoisomers of quaternary and tertiary 4-methyl piperidine analogs of hemicholinium-3 [33].

Gene context of Hemicholinium

• CHT1 is a Na(+)- and Cl(-)-dependent, hemicholinium-3 (HC-3)-sensitive, high affinity choline transporter [34].
• Neurons that synthesize acetylcholine take up choline by a recently cloned high-affinity choline transporter (choline transporter 1) that is Na+-dependent and can be blocked by hemicholinium-3 [35].
• The effects of hypothyroidism on development of cholinergic system in brain regions (prefrontal cortex and hippocampus) were evaluated by measuring choline acetyltransferase (ChAT) activity and hemicholinium-3 binding to the high-affinity choline transporter [36].
• In this study, we compared in vitro effects of soluble nonaggregated human Abeta 1-40 and 1-42 either on synaptosomal hemicholinium-3 sensitive choline carriers or on membrane fluidity in hippocampi of male and female Wistar rats aged 7 and 14 days or 2-3 months [37].
• The importance of ChoK for the regulation of cell proliferation has also been proposed since an inhibitor for this enzyme, hemicholinium-3 (HC-3), drastically reduces entry into the S phase after stimulation with growth factors [38].

Analytical, diagnostic and therapeutic context of Hemicholinium

• We compared the effects of this "depletion regimen" with the responses in two control groups: a stimulation control group, which was subjected to high-frequency right vagus stimulation only, and a drug control group, which received a hemicholinium-3 infusion only [39].
• Perfusion of 10 microM hemicholinium-3 (HC-3), a Ch uptake inhibitor, through the striatum induced a complete inhibition of ACh release and increased Ch levels in all drug-treated groups [40].
• 2. Subcutaneous injection of maximum tolerable doses of hemicholinium-3 (50 mug/kg) twice daily for 7 days increased the number of extrajunctional receptors along the whole length of muscle fibre, the approximate density of receptor on muscle membrane being increased from 6/mum2 in normal diaphragm to 38/mum2 [41].
• Central pretreatment with hemicholinium-3 also inhibited the pressor response to intravenous injection of 0.5 mg/kg cocaine [42].
• 2 In unstimulated ganglia, the uptake of [3H]-choline (0.1 microM) ('high affinity uptake') was unaffected by denervation or by hemicholinium-3 (HC-3), suggesting uptake by structures other than cholinergic nerve terminals [43].

References