Histamine

Effect of mitragynine, an indole alkaloid isolated from Thai medicinal plant kratom (Mitragyna speciosa), on electrically stimulated contraction was studied in the guinea-pig ileum. Mitragynine (1 nM - 3 μM) inhibited the ileum contraction elicited by electrical stimulation, and its pD2 value was 6.91 ± 0.04 (n = 5). Morphine (1 nM − 1 μM) also inhibited the electrically stimulated contraction in a concentration-dependent manner (pD2 7.68 ± 0.11; n = 5). Mitragynine was 10 fold less potent than morphine. Mitragynine (3–10 μM) did not show any effect on the smooth muscle contraction induced by acetylcholine or histamine. Naloxone (10–300 nM) reversed the inhibitory effect of mitragynine on electrically stimulated contraction. Furthermore, naloxone showed a shift of concentration-response curve of mitragynine to the right. There was no significant difference in the affinity of naloxone (i.e. pA2) in the presence of mitragynine or morphine. Mitragynine (3–10 μM) inhibited the naloxone-precipitated withdrawal contraction following a brief (5 min) exposure of the ileum to morphine. Tetrodotoxin (1 μM) and atropine (1 μM) inhibited the withdrawal contraction. The present results suggest that mitragynine inhibits the electrically stimulated contraction of guinea-pig ileum through the opioid receptor.

Background: Psychiatrists started using urine pyrroles (hydroxyhemopyrrolin-2-one, HPL) to diagnose psychiatric disorders many years ago. The biological origins of HPL are not known, nor are the causes of elevated urinary pyrrole excretion well understood. Methods: In the present study we analyzed the level of pyrroles in 148 patients with schizophrenia, 135 patients with bipolar disorder, 97 patients with depression, 119 patients with ADHD and compared these data with the results of pyrrole tests for patients with non-psychiatric conditions and healthy volunteers. Results: According to our data, urinary pyrrole concentrations tended to be high in patients with psychiatric disorders, but elevated level of pyrroles was not specific for only these patients. We found evidence of an allergy related component in the fact that elevated pyrrole levels were significantly more prevalent in subjects with elevated histamine values. A role of intestinal bacteria, or imbalances in intestinal bacterial metabolism, was also suggested based on the found relationship between elevated pyrrole levels and elevations in indicans and urobilinogens. In addition, our data demonstrated that subjects with severely elevated pyrrole levels were deficient in nutrients such as zinc, vitamin B3, and vitamin C. Conclusion: Thus, pyrrole excretion seems to be a component of illness in general and not strictly psychiatric disorders.

The cell line HMC-1, derived from a patient with mast cell leukaemia, is the only established cell line exhibiting a phenotype similar to that of human mast cells. This paper reports on a detailed characterization of the expression of a panel of markers for various types of immature and mature haematopoietic cells in the HMC-1. We also studied the potential of HMC-1 to differentiate upon treatment with conditioned media from the human T-cell line Mo, retinoic acid or DMSO. HMC-1 was found to express several mast cell-related markers. A high expression of Kit, the receptor for stem-cell factor, was detected. The majority of the cells were stained with a MoAb against the mast cell-specific serine protease tryptase. Of particular interest was the finding that beta-tryptase mRNA, but not alpha-tryptase mRNA, was expressed in HMC-1. Using enzyme-histochemistry we were able to show that the beta-tryptase was enzymatically active, indicating that tryptase can form active homotetramers. Bot...

Brain monoamines (serotonin, norepinephrine, dopamine, and histamine) play an important role in emotions, cognition and in pathophysiology and treatment of mental disorders. The interactions between serotonin, norepinephrine and dopamine were studied in numerous works, however, histamine system received less attention. The aim of this study was to investigate the interactions between histamine and other monoamines, using in vivo microdialys and electrophysiology. It was found that the inverse agonist of histamine-3 receptors, thioperamide, increased the firing activity of dopamine neurons in the ventral tegmental area. Selective agonist of histamine-3 receptors, immepip, reversed thiperamide-induced stimulation of firing activity of dopamine neurons. The firing rates of serotonin and norepinephrine neurons were not attenuated by immepip or thioperamide. Thioperamide robustly and significantly increased extracellular concentrations of serotonin, norepinephrine, and dopamine in the rat prefrontal cortex and slightly increased norepinephrine and dopamine levels in the tuberomammillary nucleus of the hypothalamus. It can be concluded that histamine stimulates serotonin, norepinephrine, and dopamine transmission in the brain. Modulation of firing of dopamine neurons is a key element in functional interactions between histamine and other monoamines. Antagonists of histamine-3 receptors, because of their potential ability to stimulate monoamine neurotransmission, might be beneficial in the treatment of mental disorders.

The gut microbiota is essential to health and has recently become a target for live bacterial cell biotherapies for various chronic diseases including metabolic syndrome, diabetes, obesity and neurodegenerative disease. Probiotic biotherapies are known to create a healthy gut environment by balancing bacterial populations and promoting their favorable metabolic action. The microbiota and its respective metabolites communicate to the host through a series of biochemical and functional links thereby affecting host homeostasis and health. In particular, the gastroin-testinal tract communicates with the central nervous system through the gut–brain axis to support neuronal development and maintenance while gut dysbiosis manifests in neurological disease. There are three basic mechanisms that mediate the communication between the gut and the brain: direct neuronal communication, endocrine signaling mediators and the immune system. Together, these systems create a highly integrated molecul...

The aim of the study was to evaluate the antiulcer activity of Linum usitatissimum fixed oil against aspirin-, indomethacin-, ethanol-, reserpine-, serotonin- and stress-induced gastric ulceration in rats and histamine-induced gastric ulceration in guinea pigs. Attempts were also made to evaluate the in vitro anticholinergic and antihistaminic activity and in vivo antisecretary and antiulcer activity of oil following pylorus ligation in rats. L. usitatissimum fixed oil exhibited significant antiulcer activity against different ulcerogens in experimental animal models. The fixed oil significantly inhibited acetylcholine- and histamine-induced contraction of guinea pig and rat ileums, respectively, suggesting its anticholinergic and antihistaminic activity. The oil also exhibited significant inhibitory effect on gastric secretion/total acidity and aspirin-induced gastric ulceration in pylorus-ligated rats. The lipoxygenase inhibitory, histamine antagonistic and antisecretory (anticholinergic) effects of the oil could probably have contributed towards antiulcer activity. L. usitatissimum fixed oil may be considered to be a drug of natural origin which possesses significant antiulcer activity. The present observation is the first experimental data showing antiulcer activity of L. usitatissimum fixed oil.

We examined whether neuronal proteinase-activated receptor-2 (PAR-2) may be involved in pruritus of human skin. The endogenous PAR-2 agonist tryptase was increased up to fourfold in atopic dermatitis (AD) patients. PAR-2 was markedly enhanced on primary afferent nerve fibers in skin biopsies of AD patients. Intracutaneous injection of endogenous PAR-2 agonists provoked enhanced and prolonged itch when applied intralesionally. Moreover, itch upon mast cell degranulation was abolished by local antihistamines in controls but prevailed in AD patients. Thus, we identified enhanced PAR-2 signaling as a new link between inflammatory and sensory phenomena in AD patients. PAR-2 therefore represents a promising therapeutic target for the treatment of cutaneous neurogenic inflammation and pruritus.

Aim of the review is to summarize the contemporary evidences on interactions between brain neurotransmitters and their role in pathophysiology and treatment of depression.

Introduction. Brain neurotransmitters are biological molecules responsible for signal transduction between the neurons. Mammalian brain neurotransmitters belong to the different types of biological molecules, such as amino acids (glutamate and γ-aminobutyric acid, or GABA), monoamines (serotonin: 5-HT, norepinephrine: NE, dopamine: DA, and histamine: HA),
neuropeptides (β-endorphin, neurokinin, vasopressin, and oxytocin), or nucleotides (adenosine).

Materials and Methods. The author analyzes research papers dedicated to neurotransmitters
and their functions in mood regulation and published between 1953 and 2014. The paper focuses on evaluation of data on mechanisms of interactions between different neurotransmitters and their role in development and treatment of certain mental disorders.

Results. It has been reported that different neurotransmitters, often belonging to the different
types of biological molecules, interact on behavioral, functional, system and molecular levels. These interactions play an important role in pathophysiology of brain diseases, particularly, depression and stress and anxiety-related disorders. Conclusion. Literally all existing antidepressant drugs act on monoamine systems of the brain (5-HT, NE, and DA). Although the last-generation antidepressants and mood stabilizers demonstrated higher safety and efficacy, their therapeutic potential remains limited. The brain adenosine neurotransmission is also a potential target for the future antidepressant, mood stabilizing and antipsychotic drugs. However, these drugs may have severe side effects, for example, on cardiac activity.
It is necessary to perform further research and clinical trials to find a solution to the existing
difficulties.

As drogas com ação anti-histamínica estão entre as medicações mais comumente prescritas na prática dermatológica diária, tanto em adultos como em crianças. Este artigo aborda os novos conceitos da função dos receptores de histamina (receptores H1) e discute os efeitos anti-inflamatórios dessas drogas. A segunda geração de anti-histamínicos difere da primeira geração devido a sua elevada especificidade e afinidade pelos receptores H1 periféricos e devido a seu menor efeito no sistema nervoso central, tendo como resultado menores efeitos sedativos. Embora a eficácia dos diferentes anti-histamínicos H1 (anti-H1) no tratamento de doentes alérgicos seja similar, mesmo quando se comparam anti-H1 de primeira e de segunda geração, eles são muito diferentes em termos de estrutura química, farmacologia e propriedades tóxicas. Consequentemente o conhecimento de suas características farmacocinéticas e farmacodinâmicas é importante para a melhor prática médica, especialmente em gestantes, crianças, idosos e doentes com comorbidades.