Pharmacological effects of carcinine on histaminergic neurons in the brain

Chen, Zhong; Sakurai, Eiko; Hu, Weiwei; Jin, Chunlei; Kiso, Yoshinobu; Kato, Motohisa; Watanabe, Takehiko; Wei, Er-Qing; Yanai, Kazuhiko

doi:10.1038/sj.bjp.0705978

Cited by 23 publications

(18 citation statements)

References 36 publications

(54 reference statements)

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“…However, that experiment was performed on intact animals and a different measure of stereotyped behavior was used (licking). An increase of locomotor activity by H 2 and H 3 receptor antagonists has been reported (Chen et al 2004).…”

Section: Discussionmentioning

confidence: 98%

Histaminergic Activity in a Rodent Model of Parkinson’s Disease

et al. 2009

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Rats lesioned shortly after birth with 6-OHDA have been proposed to be a near-ideal model of severe Parkinson's disease, because of non-lethality of the procedure, near-total destruction of nigrostriatal dopaminergic fibers, and near-total dopamine (DA) denervation of striatum. There are scarce data that in Parkinson's disease, activity of the central histaminergic system is increased. Therefore, the aim of this study was to determine histamine content in the brain and the effect of histamine receptor antagonists on behavior of adult rats. At 3 days after birth, Wistar rats were pretreated with desipramine (20.0 mg/kg ip) 1 h before bilateral icv administration of the catecholaminergic neurotoxin 6-OHDA (67 microg base, on each side) or saline-ascorbic acid (0.1%) vehicle (control). At 8 weeks levels of DA and its metabolites L: -3,4-dihydroxyphenylalanine (DOPAC) and homovanillic acid (HVA) were estimated in the striatum and frontal cortex by HPCL/ED technique. In the hypothalamus, hippocampus, frontal cortex, and medulla oblongata, the level of histamine was analyzed by immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped-activity) were additionally made on control and 6-OHDA neonatally lesioned rats. Effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists (e.g., S(+)chlorpheniramine, H(1); cimetidine, H(2); thioperamide, H(3) agonist) were determined. We confirmed that 6-OHDA significantly reduced contents of DA and its metabolites in the brain in adulthood. Histamine content was significantly increased in the hypothalamus, hipocampus, and medulla oblongata. Moreover, in 6-OHDA-lesioned rats behavioral response was altered mainly by thioperamide (H(3) antagonist). These findings indicate that histamine and the central histaminergic system are altered in the brain of rats lesioned to model Parkinson's disease, and that histaminergic neurons exert a modulating role in Parkinsonian 6-OHDA-lesioned rats.

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Section: Discussionmentioning

confidence: 98%

Histaminergic Activity in a Rodent Model of Parkinson’s Disease

et al. 2009

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“…The simplest derivative is carcinine (5, b-alanylhistamine), which is devoid of the carboxyl group and shows a profile of selective H3 antagonist (Chen et al 2004). In addition, the radical scavenging and the skin protection of carcinine have repeatedly been described in literature but its carbonyl quenching activity has never been reported (Babizhayev and Yegorov 2010).…”

Section: Carnosine Derivatives: Improving Oral Bioavailability and DImentioning

confidence: 99%

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

Vistoli

Carini

2012

Amino Acids

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The ability of carnosine to prevent advanced glycoxidation end products (AGEs) and advanced lipoxidation end products (ALEs) formation, on the one hand, and the convincing evidence that these compounds act as pathogenetic factors, on the other hand, strongly support carnosine as a promising therapeutic agent for oxidative-based diseases. The mechanism/s by which carnosine inhibits AGEs and ALEs is still under investigation but an emerging hypothesis is that carnosine acts by deactivating the AGEs and ALEs precursors and in particular the reactive carbonyl species (RCS) generated by both lipid and sugar oxidation. The ability of carnosine to inhibit AGEs and ALEs formation and the corresponding biological effects has been demonstrated in several in vitro studies and in some animal models. However, such effects are in line of principle, limited in humans, due to the effect of serum carnosinase (absent in rodents), which catalyzes the carnosine hydrolysis to its constitutive amino acids. Such a limitation has prompted a great interest in the design of carnosine derivatives, which maintaining (or improving) the reactivity with RCS, are more resistant to carnosinase. The present paper intends to critically review the most recent studies oriented to obtaining carnosine derivatives, optimized in terms of reactivity with RCS, selectivity (no reaction with physiological aldehydes) and the pharmacokinetic profile (mainly through an enhanced resistance to carnosinase hydrolysis). The review also includes a brief description of AGEs and ALEs as drug targets and the evidence so far reported regarding the ability of carnosine as inhibitor of AGEs and ALEs formation and the proposed reaction mechanisms.

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“…28 The training apparatus was a box consisting of a small lighted compartment (15 ϫ 10 ϫ 10 cm 3 ) and a large dark compartment (18 ϫ 12 ϫ 10 cm 3 ). A 10 ϫ 10 cm 2 guillotine door separated the two compartments.…”

Section: Step-through Passive Avoidance Testmentioning

confidence: 99%

Loss of Hrs in the Central Nervous System Causes Accumulation of Ubiquitinated Proteins and Neurodegeneration

Tamai

Toyoshima

Tanaka

et al. 2008

The American Journal of Pathology

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The endosomal sorting complex required for transport (ESCRT) proteins form multimolecular complexes that control multivesicular body formation, endosomal sorting , and transport ubiquitinated membrane proteins (including cell-surface receptors) to the endosomes for degradation. There is accumulating evidence that endosomal dysfunction is linked to neural cell degeneration in vitro, but little is known about the relationship between neural disorders and ESCRT proteins in vivo. Here we specifically deleted the hrs gene, ESCRT-0, in the neurons of mice by crossing loxP-flanked hrs mice with transgenic mice expressing the synapsin-I Cre protein (SynI-cre). Histological analyses revealed that both apoptosis and a loss of hippocampal CA3 pyramidal neurons occurred in the hrs flox/flox ;SynI-cre mice. Notably , the hrs flox/flox ;SynI-cre mice accumulated ubiquitinated proteins , such as glutamate receptors and an autophagy-regulating protein , p62. These molecules are particularly prominent in the hippocampal CA3 neurons and cerebral cortex with advancing age. Accordingly , we found that both locomotor activity and learning ability were severely reduced in the hrs flox/flox ;SynI-cre mice. These data suggest that Hrs plays an important role in neural cell survival in vivo and provide an animal model for neurodegenerative diseases that are known to be commonly affected by the generation of proteinaceous aggregates.

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Pharmacological effects of carcinine on histaminergic neurons in the brain

Cited by 23 publications

References 36 publications

Histaminergic Activity in a Rodent Model of Parkinson’s Disease

Histaminergic Activity in a Rodent Model of Parkinson’s Disease

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

Loss of Hrs in the Central Nervous System Causes Accumulation of Ubiquitinated Proteins and Neurodegeneration

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