Journal ArticleDOI
Inhibition of histamine synthesis in brain by alpha-fluoromethylhistidine, a new irreversible inhibitor: in vitro and in vivo studies.
Reads0
Chats0
TLDR
For example, alpha-Fluoromethylhistidine (α-FMH) has been used for in vitro and in vivo studies of brain histidine decarboxylase (HD) as discussed by the authors.Abstract:
alpha-Fluoromethylhistidine (alpha-FMH), a new potent inhibitor of histidine decarboxylase (HD), has been used for in vitro and in vivo studies of brain HD. Following a preincubation with (+)-alpha-FMH, brain HD activity was inhibited in a time-dependent and concentration-dependent manner. The enzyme activity was not restored by overnight dialysis against standard buffer. The (-) antimer of alpha-FMH was ineffective. When injected intraperitoneally in a single dose of 20 mg/kg, (+/-)-alpha-FMH induced a complete loss in HD activity in cerebral cortex and hypothalamus as well as in peripheral tissues, such as stomach. At a dosage of 100 mg/kg (+/-)-alpha-FMH did not alter histamine-N-methyltransferase, DOPA decarboxylase, and glutamate decarboxylase activities. The maximal decrease of HD activity occurred after 2 h in both cerebral cortex and hypothalamus, but the time course of the recovery of enzyme activity was slower in the cerebral cortex. The enzyme activity reached control value within 3 days in hypothalamus and was not fully restored after 4 days in cerebral cortex. Contrasting with the diminished HD activity, a substantial concentration of histamine remained present in five regions of mouse brain. Thus, alpha-FMH is a highly specific irreversible inhibitor of brain HD activity and its efficacy makes it useful to study the physiological role of brain histamine.read more
Citations
More filters
Journal ArticleDOI
Histamine in the Nervous System
TL;DR: Mutual interactions with other transmitter systems form a network that links basic homeostatic and higher brain functions, including sleep-wake regulation, circadian and feeding rhythms, immunity, learning, and memory in health and disease.
Journal ArticleDOI
Anatomical, Physiological, and Pharmacological Characteristics of Histidine Decarboxylase Knock-Out Mice: Evidence for the Role of Brain Histamine in Behavioral and Sleep–Wake Control
Régis Parmentier,Hiroshi Ohtsu,Zahia Djebbara-Hannas,Jean Louis Valatx,Takehiko Watanabe,Jian-Sheng Lin +5 more
TL;DR: Data indicate that disruption of HA-synthesis causes permanent changes in the cortical-EEG and sleep–wake cycle and that, at moments when high vigilance is required, mice lacking brain HA are unable to remain awake, a prerequisite condition for responding to behavioral and cognitive challenges.
Journal ArticleDOI
The Concise Guide to PHARMACOLOGY 2013/14: Enzymes
Stephen P.H. Alexander,Helen E. Benson,Elena Faccenda,Adam J. Pawson,Joanna L. Sharman,Michael Spedding,John A. Peters,Anthony J. Harmar +7 more
TL;DR: The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
Journal ArticleDOI
Suicide substrates: mechanism-based enzyme inactivators
TL;DR: Suicide substrates are defined as a class of irreversible inactivators of specific target enzymes where the target enzyme participates in its own destruction by catalytic unmasking of a latent functional group at some stage in the catalytic cycle of the enzyme.
Journal ArticleDOI
Evidence for histaminergic arousal mechanisms in the hypothalamus of cat
TL;DR: The results suggest that histaminergic systems in the hypothalamus play an important role in arousal mechanisms and their actions are mediated through H1-receptors.
References
More filters
Journal Article
Protein Measurement with the Folin Phenol Reagent
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
Journal ArticleDOI
Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]dopa in various regions of the brain.
TL;DR: It is revealed that norepinephrine and dopamine are specifically localized in complex systems of neurons in the brain, a finding which lends support to the hypothesis that both amines may be neurotransmitters in the central nervous system.
Journal ArticleDOI
Esters of Methanesulfonic Acid as Irreversible Inhibitors of Acetylcholinesterase
Richard J. Kitz,Irwin B. Wilson +1 more
Journal ArticleDOI
Selective inhibitors of biosynthesis of aminergic neurotransmitters
J. Kollonitsch,J. Kollonitsch,A. A. Patchett,A. A. Patchett,S. Marburg,S. Marburg,A. L. Maycock,A. L. Maycock,Leroy M. Perkins,Leroy M. Perkins,G. A. Doldouras,G. A. Doldouras,D. E. Duggan,D. E. Duggan,S. D. Aster,S. D. Aster +15 more
TL;DR: Examples of the transformation of amino acids into the corresponding substituted 3-fluoro-alanines, resulting in potent time-dependent decarboxylase inactivators are reported, which could be of help in elucidating the complexities of neurophysiology and neurochemistry, as well as of service in medicine by correcting pathological levels of these agonists.
Journal ArticleDOI
Isotopic microassay of histamine, histidine, histidine decarboxylase and histamine methyltransferase in brain tissue.
K. M. Taylor,Solomon H. Snyder +1 more
TL;DR: Because the methylation of histamine is uniform in brain samples studied, a single isotopic assay with [3H]S‐adenosyl‐l‐methionine as the methyl donor is possible and increases sensitivity, so that 10 pg of tissue histamine can be estimated reliably.