Enkephalins and gastrin fragments: possible existence of different analgesic mechanisms

The mechanism of analgetic action of pentagastrin, its tripeptide fragment (MAF), synthetic met- and leu-enkephalins was studied in rats. The analgetic effect of the peptides was evaluated from the tail extracting test. Also, the content of biogenic amines in the rat brain and interaction of the peptides with opiate receptors of the guinea-pig ileum were examined. It was demonstrated that analgesia induced by pentagastrin or MAF differs from that obtained after intraventricular injection of the enkephalins. The effect of the latter ones is not consequent on their interaction with classic opiate receptors. It was also discovered that pentagastrin, MAF and enkephalins produce a different action on metabolism of biogenic amines. The possibility of analgesia unmediated by specific peptide binding to opiate receptors is discussed.     

Effects of biogenic amines on the formation of adenosine 3',5'-monophosphate in human thyroid slices.

The effects of various concentrations of biogenic amines on the formation of adenosine-3', 5'-monophosphate (cyclic AMP) and their interactions with other thyroid stimulators were investigated in human thyroid slices from normal and Graves' disease. Most of biogenic amines were found to have the stimulatory effects to some extent. Among the biogenic amines tested, histamine was the most potent thyroid stimulator, norepinephrine and serotonin, the intermediate in terms of cyclic AMP formation. The effect of histamine was almost as potent as TSH in thyroid slices from Graves' disease. This stimulatory effect of histamine was blocked by metiamide, a histamine H2-receptor antagonist, but not by chlorpheniramine, a histamine H1-receptor antagonist. The effect of norepinephrine was completely inhibited by propranolol, but not by phentolamine. Polyphloretin phosphate did not inhibit norepinephrine- or histamine-induced cyclic AMP formation, while it significantly depressed cyclic AMP formation induced by prostaglandin E2. The maximal effect of histamine was additive to that of TSH. It is suggested that biogenic amines, histamine and norepinephrine, in particular, have the thyroid receptors different from that of TSH or prostaglandin E2 and could play an important role in thyroid physiology.     

Effects of biogenic amines on the formation of adenosine 3', 5'-monophosphate in human thyroid slices.

The effects of various concentrations of biogenic amines on the formation of adenosine-3', 5'-monophosphate (cyclic AMP) and their interactions with other thyroid stimulators were investigated in human thyroid slices from normal and Graves' disease. Most of biogenic amines were found to have the stimulatory effects to some extent. Among the biogenic amines tested, histamine was the most potent thyroid stimulator, norepinephrine and serotonin, the intermediate in terms of cyclic AMP formation. The effect of histamine was almost as potent as TSH in thyroid slices from Graves' disease. This stimulatory effect of histamine was blocked by metiamide, a histamine H2-receptor antagonist, but not by chlorpheniramine, a histamine H1-receptor antagonist. The effect of norepinephrine was completely inhibitied by propranolol, but not by phentolamine. Polyphloretin phosphate did not inhibit norepinephrine- or histamine-induced cyclic AMP formation, while it significantly depressed cyclic AMP formation induced by prostaglandin E2. The maximal effect of histamine was additive to that of TSH. It is suggested that biogenic amines, histamine and norepinephrine, in particular, have the thyroid receptors different from that of TSH or prostaglandin E2 and could play an important role in thyroid physiology.     

Molecular and pharmacological properties of insect biogenic amine receptors: lessons from Drosophila melanogaster and Apis mellifera

In the central nervous system (CNS) of both vertebrates and invertebrates, biogenic amines are important neuroactive molecules. Physiologically, they can act as neurotransmitters, neuromodulators, or neurohormones. Biogenic amines control and regulate various vital functions including circadian rhythms, endocrine secretion, cardiovascular control, emotions, as well as learning and memory. In insects, amines like dopamine, tyramine, octopamine, serotonin, and histamine exert their effects by binding to specific membrane proteins that primarily belong to the superfamily of G protein-coupled receptors. Especially in Drosophila melanogaster and Apis mellifera considerable progress has been achieved during the last few years towards the understanding of the functional role of these receptors and their intracellular signaling systems. In this review, the present knowledge on the biochemical, molecular, and pharmacological properties of biogenic amine receptors from Drosophila and Apis will be summarized. Arch.     

Electrical responses of salivary gland cells of the gastropod mollusc Philine aperta to putative neurotransmitters—II. Octopamine, 5-HT and other biogenic amines

1. Intracellular recordings were made from salivary gland cells of the mollusc Philine aperta. Salivary cell action potentials were produced in a dose-dependent manner in response to bath-application of octopamine, 5-hydroxytryptamine (5-HT) and certain related biogenic amines.2. Evidence that amines act on presynaptic receptors on nerve terminals rather than directly on gland cell receptors is presented. These receptors may serve to modulate salivary neuroglandular transmission.3. Octopamine and 5-HT action was reversibly blocked or reduced by the antagonists phentolamine, chlorpromazine, cyproheptidene, yohimbine, D-tubocurarine, hexamethonium and atropine.     

The paraventricular organ of mormyrid fish: uptake or release of intraventricular biogenic amines?

The paraventricular organ of Gnathonemus petersii was investigated with light and electronmicroscopical techniques. It contains high concentrations of dopamine, noradrenaline and serotonin, but the synthesizing enzymes are not or hardly present. Consequently, the cerebrospinal fluid-contacting neurons might pick up their biogenic amines from the ventricular fluid. Dense subependymal axonal plexuses in the everted telencephalon probably release these substances into the ventricle. However, electronmicroscopical observations suggest release rather than uptake by the paraventricular organ. The possible significance of intraventricular release, transport and uptake of biogenic amines is discussed.     

Identification of CC chemokine receptor 7 residues important for receptor activation

The binding pocket of family A GPCRs that bind small biogenic amines is well characterized. In this study we identify residues on CC chemokine receptor 7 (CCR-7) that are involved in agonist-mediated receptor activation but not in high affinity ligand binding. The mutations also affect the ability of the ligands to induce chemotaxis. Two of the residues, Lys3.33(137) and Gln5.42(227), are consistent with the binding pocket described for biogenic amines, while Lys3.26(130) and Asn7.32(305), are found at, or close to, the cell surface. Our observations are in agreement with findings from other peptide and chemokine receptors, which indicate that receptors that bind larger ligands contain contact sites closer to the cell surface in addition to the conventional transmembrane binding pocket. These findings also support the theory that chemokine receptors require different sets of interactions for high affinity ligand binding and receptor activation.     

Long-term control of neuronal excitability by corticosteroid hormones

Hippocampal CA1 neurons express both mineralocorticoid and glucocorticoid receptors. Due to the difference in affinity of the two receptor types for corticosterone and variations in endogenous steroid levels, occupation of the receptors will range between a situation of predominant mineralocorticoid receptor activation and conditions where both receptor types are occupied. It was observed that local signal transduction is regulated by activation of the corticosteroid receptors. Particularly, transmission mediated by biogenic amines appears to be sensitive to steroid control. The data indicate that cholinergic and serotonergic responses are small with predominant mineralocorticoid receptor activation, while additional glucocorticoid receptor activation results in large responses; the reverse has been found for noradrenalin. The steroid-dependent control over transmission by biogenic amines will influence local excitability and therefore functional processes in which the hippocampal system is involved.     

Role of some biogenic amines in the pathomechanism of glomerulonephritis. I. Histological examinations of kidneys in acute and chronic serum sickness in rabbits

Investigations were carried out on the role of biogenic amines in the development of glomerulonephritis in rabbits using the experimental model of acute and chronic serum sickness. The animals immunized with foreign-species albumin received additionally 5HT and some of them were given reserpine or PCPA for reducing the level of biogenic amines. The results of histological examinations demonstrated a clear cut inhibitory effect of PCPA and reserpine on the development of inflammatory changes in the glomeruli, and their intensification with simultaneous 5HT administration. The obtained results seem to suggest a significant role of biogenic amines in the pathogenesis of inflammatory lesions developing in renal glomeruli in acute or chronic serum sickness in rabbits.     

Cloning and expression pattern of a putative octopamine/tyramine receptor in antennae of the noctuid moth <Emphasis Type="Italic">Mamestra brassicae</Emphasis>

In insects, biogenic amines have been shown to play an important role in olfactory plasticity. In a first attempt to decipher the underlying molecular mechanisms, we report the molecular cloning and precise expression pattern of a newly identified octopamine/tyramine-receptor-encoding gene in the antennae of the noctuid moth Mamestra brassicae (MbraOAR/TAR). A full-length cDNA has been obtained through homology cloning in combination with rapid amplification of cDNA ends/polymerase chain reaction; the deduced protein exhibits high identities with previously identified octopamine/tyramine receptors in other moths. In situ hybridization within the antennae has revealed that MbraOAR/TAR is expressed at the bases of both pheromone-sensitive and non-sensitive olfactory sensilla and in cells with a neurone-like shape. In accordance with previous physiological studies that have revealed a role of biogenic amines in the electrical activity of the receptor neurones, our results suggest that biogenic amines (either octopamine or tyramine) target olfactory receptor neurones to modulate olfactory coding as early as the antennal level.     

Biogenic amine production by lactic acid bacteria isolated from cider

AIMS: To study the occurrence of histidine, tyrosine and ornithine decarboxylase activity in lactic acid bacteria (LAB) isolated from natural ciders and to examine their potential to produce detrimental levels of biogenic amines. METHODS AND RESULTS: The presence of biogenic amines in a decarboxylase synthetic broth and in cider was determined by reversed-phase high-performance liquid chromatography (RP-HPLC). Among the 54 LAB strains tested, six (five lactobacilli and one oenococci) were biogenic amine producers in both media. Histamine and tyramine were the amines formed by the LAB strains investigated. Lactobacillus diolivorans were the most intensive histamine producers. This species together with Lactobacillus collinoides and Oenococcus oeni also seemed to produce tyramine. No ability to form histamine, tyramine or putrescine by Pediococus parvulus was observed, although it is a known biogenic amine producer in wines and beers. CONCLUSIONS: This study demonstrated that LAB microbiota growing in ciders had the ability to produce biogenic amines, particularly histamine and tyramine, and suggests that this capability might be strain-dependent rather than being related to a particular bacterial species. SIGNIFICANCE AND IMPACT OF THE STUDY: Production of biogenic amines by food micro-organisms has continued to be the focus of intensive study because of their potential toxicity. The main goal was to identify the microbial species capable of producing these compounds in order to control their presence and metabolic activity in foods.     

Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors

Trace amines are endogenous compounds structurally related to classical biogenic amines that have been studied for decades, triggered by their link to psychiatric conditions of high epidemiological and economical relevance. The understanding of their pharmacology on the molecular level was hampered until the recent discovery of trace-amine-specific receptors. We completed the identification of all members of this novel GPCR family in human, chimpanzee, rat, and mouse and observed remarkable interspecies differences, even between human and chimpanzee. The analysis of the chromosomal localizations, phylogenetic relationships, and ligand pocket vectors reveals three distinct receptor subfamilies. As most of these receptors do not respond to trace amines, each subfamily will presumably have a distinct pharmacological profile, which remains to be identified. We propose a uniform nomenclature describing this novel GPCR family in all mammalian species as trace-amine-associated receptors (TAARs), which resolves the ambiguities and contradictions of the previous naming.     

Dopamine and octopamine influence avoidance learning of honey bees in a place preference assay

Biogenic amines are widely characterized in pathways evaluating reward and punishment, resulting in appropriate aversive or appetitive responses of vertebrates and invertebrates. We utilized the honey bee model and a newly developed spatial avoidance conditioning assay to probe effects of biogenic amines octopamine (OA) and dopamine (DA) on avoidance learning. In this new protocol non-harnessed bees associate a spatial color cue with mild electric shock punishment. After a number of experiences with color and shock the bees no longer enter the compartment associated with punishment. Intrinsic aspects of avoidance conditioning are associated with natural behavior of bees such as punishment (lack of food, explosive pollination mechanisms, danger of predation, heat, etc.) and their association to floral traits or other spatial cues during foraging. The results show that DA reduces the punishment received whereas octopamine OA increases the punishment received. These effects are dose-dependent and specific to the acquisition phase of training. The effects during acquisition are specific as shown in experiments using the antagonists Pimozide and Mianserin for DA and OA receptors, respectively. This study demonstrates the integrative role of biogenic amines in aversive learning in the honey bee as modeled in a novel non-appetitive avoidance learning assay.     

一种利用RT-HPLC分析乳酸菌产生物胺的方法

具有脱羧酶活性的乳酸菌可通过氨基酸的脱羧反应产生具有潜在安全风险的生物胺。本文利用脱羧酶培养基初步筛查61株乳酸菌产生物胺情况,再通过RT-HPLC法测定其在发酵液和发酵乳中的生物胺含量。用10%的三氯乙酸提取样品中的生物胺,采用苯甲酰氯衍生处理后,以甲醇/水为流动相,进行梯度洗脱,流速0.8mL/min,紫外检测器波长为254nm。结果显示,组胺和酪胺得到良好的分离,在给定的浓度范围内呈现良好的线性关系(R20.995)。在发酵液和发酵乳中添加生物胺混合标准溶液,平均回收率为97.92%-101.14%,相对偏差RSD5%。结果表明,发酵液与发酵乳中生物胺的RT-HPLC法,是一种快捷、稳定、灵敏度高的检测方法,其与脱羧酶培养基法结合可以准确地实现对乳酸菌产生物胺的评价。     

Phenolamine-dependent adenylyl cyclase activation in Drosophila Schneider 2 cells

Drosophila Schneider 2 (S2) cells are often employed as host cells for non-lytic, stable expression and functional characterization of mammalian and insect G-protein-coupled receptors (GPCRs), such as biogenic amine receptors. In order to avoid cross-reactions, it is extremely important to know which endogenous receptors are already present in the non-transfected S2 cells. Therefore, we analyzed cellular levels of cyclic AMP and Ca2+, important second messengers for intracellular signal transduction via GPCRs, in response to a variety of naturally occurring biogenic amines, such as octopamine, tyramine, serotonin, histamine, dopamine and melatonin. None of these amines (up to 0.1 mM) was able to reduce forskolin-stimulated cyclic AMP production in S2 cells. Furthermore, no agonist-induced calcium responses were observed. Nevertheless, the phenolamines octopamine (OA) and tyramine (TA) induced a dose-dependent increase of cyclic adenosine monophosphate (AMP) production in S2 cells, while serotonin, histamine, dopamine and melatonin (up to 0.1 mM) did not. The pharmacology of this response was similar to that of the octopamine-2 (OA2) receptor type. In addition, this paper provides evidence for the presence of an endogenous mRNA encoding an octopamine receptor type in these cells, which is identical or very similar to OAMB. This receptor was previously shown to be positively coupled to adenylyl cyclase.     

The effect of treating method of game on the content of biogenic amines in wild duck (Anas platyrhynchos) meat during the course of storage

The aim of present study was to assess the correlation between the method of treating the carcasses of shot wild ducks (Anas platyrhynchos) and the formation of biogenic amines in the their muscles. The carcasses of wild ducks (n?=?180) were divided into three groups of 60 carcasses according to the method of treatment: eviscerated, drawn, and left untreated. Each group was further divided into three subgroups of 20 duck carcasses on the basis of the storage temperature (0, 7, and 15 °C) and stored for 21 days. Samples of breast and thigh muscles were taken at regular weekly intervals. Biogenic amines (cadaverine, putrescine, tyramine, histamine, phenylethylamine, and tryptamine) in samples of breast and thigh muscles were separated by reverse-phase liquid chromatography and detected by tandem mass spectrometry. The sum of biogenic amines was compared with a value of 5 mg/kg, indicating the critical content for fresh meat of high hygienic quality. The results of this study indicated that the sum of biogenic amines in wild duck meat exceeded this limit in an extremely short period of time after the commencement of storage (during the first week of storage). Higher content of biogenic amines were recorded in thigh muscle compared to breast muscle of drawn ducks and untreated ducks. According to our results, the generally recommended method for treating the carcasses of feathered game after hunting (evisceration) does not represent a method that would ensure a longer period of freshness or higher hygiene quality of the game than the other two possible methods of treatment from the biogenic amines point of view.     

Evolution of microbial populations and biogenic amine production in dry sausages produced in Southern Italy

AIMS: To evaluate the occurrence and evolution of biogenic amines during ripening of fermented sausages and their relationship with physico-chemical and microbiological properties of the product. METHODS AND RESULTS: Salsiccia and Soppressata were obtained from artisanal and industrial plants in Basilicata and pH, aW, microbial counts and biogenic amine content were measured. A high variability in amine content was observed. 2-Phenylethylamine and histamine were rarely found, while the tyramine, putrescine and cadaverine content increased during ripening. No correlation was found between individual biogenic amine content, microbial counts or physico-chemical parameters. CONCLUSION: Starter cultures did not necessarily prevent the production of biogenic amines whose total contents were usually higher in Soppressata, a product with a larger diameter and aW compared with Salsiccia. SIGNIFICANCE AND IMPACT OF THE STUDY: Literature findings on biogenic amine content and the evolution of microbial populations were confirmed. Normal ranges for amine content in Salsiccia and Soppressata are reported.     

Biogenic amines in the two-spotted spider mite

Whole body extracts of the two-spotted spider mite (Tetranychus urticae Koch) were analyzed using a 16-channel electrochemical array high performance liquid chromatography (HPLC)-based detection system that allows the simultaneous isolation and identification of a variety of biogenic amines. The spider mite extracts were found to contain the biogenic amines octopamine, dopamine, and 5-hydroxytryptamine (5-HT), as well as several precursors and metabolites including tyrosine, tyramine, tryptophan, and N-acetyl octopamine. Differences in the levels of biogenic amines were observed between eggs and the adult stages and between males and females. This is the first direct determination of biogenic amines in the Tetranychidae and the first demonstration of 5-HT in any mite species. © 1994 Wiley-Liss, Inc.     

Neuro-endocrine correlates of ovarian development and egg-laying behaviors in the primitively eusocial wasp (Polistes chinensis)

To explore the roles of biogenic amines in reproduction in workers in primitively eusocial societies, correlations between brain levels of biogenic amines and ovarian development or oviposition in workers of the paper wasp Polistes chinensis were investigated. Several workers in queenright colonies developed ovaries and were potential egg-layers. Maximum ovarian width was significantly correlated with brain levels of dopamine, serotonin and their metabolites (N-acetyldopamine and N-acetylserotonin). Individuals with developed ovaries proceeded with yolk formation had significantly higher levels of brain dopamine, serotonin and N-acetyldopamine compared with individuals with undeveloped ovaries. Brain dopamine levels were higher in egg-laying individuals than in other individuals with developed ovaries. Thus, the workers of the paper wasp showed quantitative differences in brain dopamine levels correlated with reproduction. These results suggest that the brain levels of biogenic amines in paper wasp workers correspond to their tasks, and that there is a mechanism for promoting reproduction by dopamine, as previously reported in the workers of eusocial bees.     

Degradation of biogenic amines by vineyard ecosystem fungi. Potential use in winemaking

Aims: To evaluate the ability of grapevine ecosystem fungi to degrade histamine, tyramine and putrescine in synthetic medium and in wines. Methods and Results: Grapevine and vineyard soil fungi were isolated from four locations of Spain and were subsequently identified by PCR. A total of 44 fungi were evaluated for in vitro amine degradation in a microfermentation system. Amine degradation by fungi was assayed by reversed‐phase (RP)‐HPLC. All fungi were able to degrade at least two different primary amines. Species of Pencillium citrinum, Alternaria sp., Phoma sp., Ulocladium chartarum and Epicoccum nigrum were found to exhibit the highest capacity for amine degradation. In a second experiment, cell‐free supernatants of P. citrinum CIAL‐274,760 (CECT 20782) grown in yeast carbon base with histamine, tyramine or putrescine, were tested for their ability to degrade amines in three different wines (red, white and synthetic). The highest levels of biogenic amine degradation were obtained with histamine‐induced enzymatic extract. Conclusion: The study highlighted the ability of grapevine ecosystem fungi to degrade biogenic amines and their potential application for biogenic amines removal in wine. Significance and Impact of Study: The fungi extracts described in this study may be useful in winemaking to reduce the biogenic amines content of wines, thereby preventing the possible adverse effects on health in sensitive individuals and the trade and export of wine.