Begriffserklärungen:

- Agmatin und Arginin, ZUSAMMENHÄNGE

- Polyamine, dazu gehören: Spermidin, Spermin und ihr ‚Vorläufer‘ Putrescin

- Synthesewege

- Harnstoff, Harnstoffzyklus

- Mitochondrien

- Pfortader, Hepatozyten

- Glutamatzyklus

[1998] Agmatine: an endogenous ligand at imidazoline receptors may be a novel neurotransmitter in brain

·       [1995] Agmatine (decarboxylated arginine) is synthesized and stored in astrocytes

·       Astrozyten

·       EXKURS: Cholesterin, Acetyl-CoA, Citratzyklus, Acetessigsäure, Ketonkörper, Ketogene Diät

[2006] Expression of arginine decarboxylase in brain regions and neuronal cells

·       [1998] Regional localization of agmatine in the rat brain: an immunocytochemical study

·       [2001] Localization of agmatine in vasopressin and oxytocin neurons of the rat hypothalamic paraventricular and supraoptic nuclei

·       Vasopressin (syn. Argininvasopressin, ADH, Antidiuretisches Hormon) und Oxytocin 

[2007] Agmatine : metabolic pathway and spectrum of activity in brain

[2008] Regulatory mechanisms underlying agmatine homeostasis in humans

·       [2003] Gastrointestinal uptake of agmatine: distribution in tissues and organs and pathophysiologic relevance

[2014] Arginine decarboxylase and agmatinase: an alternative pathway for de novo biosynthesis of polyamines for development of mammalian conceptuses

·       „…‘the product of conception at any point between fertilization and birth.‘ …“

[2016] Altered brain arginine metabolism in schizophrenia

·       Präpulsinhibition / Prepulse inhibition 

·       COMT

·       Circulus arteriosus cerebri

·       Schreckreaktion / Startle response

·       Sensorisches Gating / Sensory gating

·       BA8 = The frontal eye field / Frontales Augenfeld

·       [2002] The GABAergic system in schizophrenia

·       [2009] The dopamine hypothesis of schizophrenia: version III--the final common pathway

·       [2012] A new target for diagnosis and treatment of CNS disorders: agmatinergic system

·       „…It has been suggested that agmatine has analgesic, anxiolytic and antidepressant activities in animals. …“

·       [2013] Increased plasma agmatine levels in patients with schizophrenia

·       „Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. …“

·       [2003] Is the arginine-nitric oxide pathway involved in the pathogenesis of schizophrenia?

·       „…There are various evidences of the role of the nitric oxide (NO) in several neuropsychiatric disorders including schizophrenia. … Plasma arginase activities and Mn* were found to be significantly lower and total nitrite level higher in patients with schizophrenia compared with controls. Our results suggest that the arginine-NO pathway is involved in the pathogenesis of schizophrenia.“ * Mn = Manganese / Mangan

·       [2000] Is agmatine a novel neurotransmitter in brain?

·       „Recent evidence suggests that agmatine, which is an intermediate in polyamine biosynthesis, might be an important neurotransmitter in mammals. Agmatine is synthesized in the brain, stored in synaptic vesicles in regionally selective neurons, accumulated by uptake, released by depolarization, and inactivated by agmatinase. … As a result of its ability to inhibit both hyperalgesia and tolerance to, and withdrawal from, morphine, and its neuroprotective activity, agmatine has potential as a treatment of chronic pain, addictive states and brain injury.“

·       Agmatin: „Natürliche Vorkommen sind aus Mutterkorn, dem Korbblütler Ambrosia artemisiifolia, der Seeanemone Anthopleura japonica und Heringssamen bekannt.“

·       Mutterkorn -> Ergotamin

·       Sheehan-Syndrom / Sheehan’s syndrome

·       [2010] Eye tracking dysfunction in schizophrenia: characterization and pathophysiology -> A ‚behavioral‘ deficit …? – S.o.: BA8 …

·       [1989] Free amino acid level determinations in normal and schizophrenic brain

·       [1994] Agmatine: an endogenous clonidine-displacing substance in the brain

·       „…Agmatine binds to alpha 2-adrenergic and imidazoline receptors and stimulates release of catecholamines from adrenal chromaffin cells. Its biosynthetic enzyme, arginine decarboxylase, is present in brain. Agmatine, locally synthesized, is an endogenous agonist at imidazoline receptors, a noncatecholamine ligand at alpha 2-adrenergic receptors and may act as a neurotransmitter.“

·       [2012] Agmatinase, an inactivator of the putative endogenous antidepressant agmatine, is strongly upregulated in hippocampal interneurons of subjects with mood disorders

·       „…The reported increased expression of agmatinase suggests a functional relevance of the enzyme in the pathophysiology of human affective disorders. This article is part of a Special Issue entitled 'Anxiety and Depression'.“

·       [2003] Vertebrate agmatinases: what role do they play in agmatine catabolism?

·       [2020] Insights into the Mn2+ Binding Site in the Agmatinase-Like Protein (ALP): A Critical Enzyme for the Regulation of Agmatine Levels in Mammals

[2018] The antizyme family for regulating polyamines

[2019] Dietary and Gut Microbiota Polyamines in Obesity- and Age-Related Diseases

·       [2011] Polyamines in foods: development of a food database

·       [2014] The molecular and metabolic influence of long term agmatine consumption

·       [2018] Arginase 2 Suppresses Renal Carcinoma Progression via Biosynthetic Cofactor Pyridoxal Phosphate Depletion and Increased Polyamine Toxicity

[2021] Alzheimer's disease as a chronic maladaptive polyamine stress response

·       „…Their transient synthesis is induced by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response (PSR). …“

[2022] Unique Chemistry, Intake, and Metabolism of Polyamines in the Central Nervous System (CNS) and Its Body

·       (1) It summarizes the role of most natural and some important synthetic PAs.

·       (2) It depicts PA uptake from nutrition and bacterial production in the intestinal system following loss of PAs via defecation.

·       (3) It highlights the discrepancy between the high concentrations of PAs in the gut lumen and their low concentration in the blood plasma and cerebrospinal fluid, while concentrations in cellular cytoplasm are much higher.

·       (4) The present review provides a novel and complete scheme for the biosynthesis of PAs, including glycine, glutamate, proline and others as PA precursors, and provides a hypothesis that the agmatine pathway may rescue putrescine production when ODC knockout seems to be lethal (solving the apparent contradiction in the literature).

·       (5) It summarizes novel data on PA transport in brain glial cells explaining why these cells but not neurons preferentially accumulate PAs.

·       (6) Finally, it provides a novel and complete scheme for PA interconversion, including hypusine, putreanine, and GABA (unique gliotransmitter) as end-products. …

-> Alternate pathway for GABA biosynthesis …

·       „…This alternate pathway for GABA biosynthesis (Figure 3) is known to occur in midbrain dopamine neurons and may be of special importance for the release of GABA by astrocytes.“

-> Diamine oxidase …

·       „…an enzyme involved in the metabolism, oxidation, and inactivation of histamine and other polyamines such as putrescine or spermidine in animals. …

·       Lowered diamine oxidase values in maternal blood in early pregnancy might be an indication for trophoblast-related pregnancy disorders like early-onset preeclampsia. …“

-> 4-aminobutanal – s. dazu:

[2007] The concept of "aldehyde load" in neurodegenerative mechanisms: cytotoxicity of the polyamine degradation products hydrogen peroxide, acrolein, 3-aminopropanal, 3-acetamidopropanal and 4-aminobutanal in a retinal ganglion cell line

·       Reactive aldehyde species [RASP]

·       [2016] The transporter and permeability interactions of asymmetric dimethylarginine (ADMA) and L-arginine with the human blood-brain barrier in vitro

·       [2012] Interaction of the cardiovascular risk marker asymmetric dimethylarginine (ADMA) with the human cationic amino acid transporter 1 (CAT1)

·       ADMA

·       [1999] GABAergic system in the developing mammalian retina: dual sources of GABA at early stages of postnatal development

·       [2014] Arginine decarboxylase and agmatinase: an alternative pathway for de novo biosynthesis of polyamines for development of mammalian conceptuses (s.a.o.)

Und bitte nicht vergessen:

Neue ‚Konzepte‘ wären hilfreich -> Siehe: Aktuelles …

Fazit