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[EEG and biochemical considerations on 40 cirrhotic patients surgically treated by portacaval anastomosis or mesenterico-caval bypass].

Starting from biochemical hypotheses on hepatic encephalopathy, which presuppose at the basis of this disease first of all some modifications of the plasmatic values of octopamine, ammonia, serotonin and of particular aromatic aminoacids, the Authors compared the levels of ammoniemia and of octopaminemia with eegraphic data, in two groups of cirrhotic patients, operated of porto-cava anastomosis (16 patients) ad of mesenterico-cava by-pass (24 patients). All this in order to value if there are significant correlations between these values and the cerebral damage and also if there are differences between the two types of operation. Attained data show a good correlation between neuropsychiatric symptomatology and importance of the cerebral damage noticeable at the E.E.G. As to the possible correlations existing between biochemical data and E.E.G., while as to plasmatic octopamine no significant modifications were found, as to ammoniemia, highest values correspond to findings of greater cerebral compromission. Moreover, it seems that between the two types of operations, the mesenterico-cava by-pass is the one that allows a better clinical and eegraphic evolution.

Amino Acids↗

Deranged tyrosine metabolism in cirrhosis.

In normal individuals, the main route for tyrosine degradation is the hepatic pathway tyrosine→4-hydroxyphenylpyruvic acid→homogentisic acid→CO(2). Quantitatively minor pathways, in large part extrahepatic, are: tyrosine→tyramine→octopamine and tyrosine→dopa→catecholamines.In cirrhosis, the main hepatic pathway is blocked to varying degrees at the first three stages. This appears to be due to lack of activity of the enzymes tyrosine transaminase, PHPA oxidase, and HGA oxidase, the first step being rate limiting. Hypertyrosinemia and tyrosine intolerance result.With the main hepatic pathway partially blocked, an abnormally large amount of tyrosine passes into the normally minor extrahepatic pathway leading to the false neurotransmitters tyramine and octopamine. Overproduction of these amines ensues and they accumulate in the body fluid.The false neurotransmitters can displace catecholamines from their storage sites in the peripheral and central nervous system, and thereby disrupt adrenergic processes in arterioles, kidneys, and brain. Their accumulation in cirrhotic patients may play a role in the pathogenesis of hepatic encephalopathy, hepatorenal syndrome, and hyperdynamic circulation.

4-Hydroxyphenylpyruvate Dioxygenase↗

[Study of maximal response of the rat vas deferens. I - study of adrenergic amines with diverse mechanisms of action and the influence of cast concentration in the physiological solution].

As a preliminary to research on phenomena connected with the appearance of maximal responses in the isolated rat vas deferens greater than those obtainable with noradrenaline, the responses to noradrenaline, octopamine and thyramine under various experimental conditions are discussed. Octopamine give maximal responses which are consistently greater than those with noradrenaline but the differences are scarcely significant. Variation of the Ca2+ concentration in the physiological solution affects response to the three amines in a different way. It appears that when there is an indirect component in the mechanism of action, lack of Ca2+ has less effect on the activity of the compound.

Animals↗

Analysis of cyclic boronated and trimethylsilylated phenolalkylamines by gas chromatography and electron impact mass spectrometry

The side chain of phenolalkylamines containing a bifunctional group was derivatized as the cyclic boronate, and then the residual phenolic group was trimethylsilylated. The resulting derivatives were single reaction products in each case, with good gas chromatographic properties and informative mass spectra to afford prominent molecular ions by gas chromatography with electron impact mass spectrometry (GC/EI-MS). The cyclic boronated-trimethylsilylated derivatives yielded the isotope pattern for boron ((10)B:(11)B =-1:4.2) and characteristic ions [M](+), [M - H](+), [M - CH(3)](+), [M - RBO](+), [M - TMSO](+), and [M - TMSO - C(6)H(5)](+) ions in the mass spectra. In order to distinguish between m- and p-phenolalkylamines, the mass spectra of the cyclic phenylboronated-trimethylsilylated (PBA-TMS) derivatives were compared with those of the trimethylsilylated (TMS) derivatives. The TMS derivatives of octopamine (p-) and norfenefrine (m-) showed identical mass spectra, while the PBA-TMS derivatives had mass spectra sufficiently different from one other to distinguish between the isomers. The most prominent ion of the PBA-TMS derivative is the [M - H](+) ion (m/z 310) for octopamine and the [M](+) ion (m/z 311) for norfenefrine. Copyright 1999 John Wiley & Sons, Ltd.

Journal Article↗

Enantioselectivity of basic analytes in CZE enantioseparation under reversed-polarity mode using sulfated beta-cyclodextrins as chiral selectors: An unusual temperature effect.

Temperature effects on the enantioselectivity of basic analytes in CZE enantioseparation were studied under reversed-polarity mode using randomly sulfate-substituted beta-CDs (MI-S-beta-CD) as chiral seletors. Two catecholamines (epinephrine and isoproterenol) and two structurally related compounds (octopamine and norephedrine) were selected as test compounds in an electrophoretic system at low pH. The mobility differences between the (+)-enantiomers and the (-)-enantiomers of the two catecholamines and dopamine at 40 degrees C are greater than those at 25 degrees C with MI-S-beta-CD, even at a concentration as low as 0.3% w/v. Thus the enantioselectivity of these three basic analytes increases with increasing temperature. This phenomenon results from the inequality of the temperature effect on the mobility of the two enantiomers. In contrast, norephedrine behaves differently. The (+)-enantiomers of these basic analytes were found to migrate faster than the (-)-enantiomers. Consequently, the unusual temperature effect on the enantioselectivity can be observed when the mobility difference of the (+)-enantiomer between 40 and 25 degrees C is greater than that of the (-)-enantiomer using MI-S-beta-CD at a concentration greater than about 0.7% w/v for enantioseparation of isoproterenol, 0.4% w/v for epinephrine, and 0.3% w/v for octopamine. This unusual temperature effect offers the advantages to enhance enantioselectivity, to improve enantioseparation, and to reduce migration times.

Catecholamines↗

Circadian efferent input to Limulus eyes: anatomy, circuitry, and impact.

Much is known about the anatomy of Limulus retinal efferent neurons and the structural and functional consequences of their activation. Retinal efferent axons arise from cell bodies located in the cheliceral ganglia of the brain, and they project out all of the optic nerves. Their unique neurosecretory-like terminals contact all cell types in lateral eye ommatidia, the retinular cells of the median eye, and the internal rhabdom of ventral photoreceptors. Lateral and median rudimentary photoreceptors are also innervated. The activity of the efferents is circadian. They are active during the subjective night and inactive during the subjective day. Activation of the efferents drives dramatic and diverse changes in the structure and function of Limulus eyes and causes the sensitivity and responsiveness of the eyes to light to increase at night. Relatively little is known about the molecular mechanisms that produce these structural and functional changes, but one efferent-activated biochemical cascade has been identified. The biogenic amine octopamine is released from efferent terminals, and an octopamine-stimulated rise in cAMP in photoreceptors, with a subsequent activation of cAMP-dependent protein kinase, mediates many of the known effects of efferent input. A photoreceptor-specific protein, myosin III, is phosphorylated in response to efferent input; this protein may play a role in the efferent stimulated changes in photoreceptor structure and function. Anatomical, biophysical, biochemical, and molecular approaches are now being effectively combined in studies of Limulus eyes; thus, this preparation should be particularly useful for further detailed investigations of mechanisms underlying the modulation of primary sensory cells by efferent input.

Animals↗

Axonal transport of [3H] GABA and [3H] glutamate in excitatory and inhibitory neurons innervating lobster exoskeletal musculature.

This paper describes the results of intracellular injections of radiolabelled neurotransmitters and transmitter precursor substances, including glutamate, GABA, aspartate, octopamine, tyramine, tryptophan, and choline, into cell bodies of identified excitatory and inhibitory neurons innervating lobster extensor musculature. The distributions and identities of radioactive substances appearing in axons were examined at various times following injection and in vitro incubation. Injected GABA and glutamate were found in appreciable quantities in both excitatory and inhibitory axons and migrated down axons at an estimated rate of between 16 and 22 mm/day at 12 degrees C, whereas the other substances tested were present in substantially smaller quantities and migrated at an estimated rate of less than 7.5 mm/day at 12 degrees C. Injected GABA, D-glutamate and L-glutamate accumulated proximal to ligatures tied around nerves, whereas neither octopamine nor aspartate accumulated proximal to ligatures. Since GABA is the transmitter substance released by inhibitory neurons and L-glutamate is thought to be released from excitatory nerve terminals, these results are consistent with the suggestion that amino acids serving as neurotransmitters are axonally transported. The specificity of axonal transport does not appear to be restricted to the cognate neurotransmitter, as indicated by the movement of L-glutamate in inhibitory axons and GABA in excitatory axons and of D-glutamate in both excitatory and inhibitory axons, but rather may be relaxed to include substances closely related to the neurotransmitter. Some restrictions, however, are apparently placed on axonal transport of small charged molecules in these neurons in that other substances tested migrated down nerves at a considerably slower rate.

Animals↗

Activation of DUM cell interneurons by ventral giant interneurons in the cockroach, Periplaneta americana.

Dorsal unpaired median (DUM) cells in orthopteran insects are known to contain the neuromodulatory substance octopamine, and DUM cells with peripheral axons augment synaptic activity at neuromuscular junctions. One of the most studied systems in the cockroach is the giant interneuron (GI) system which controls the initial movements of a wind-mediated escape response. Our data demonstrate that DUM cells that are restricted to the central nervous system (DUM interneurons) receive inputs from ventral giant interneurons (vGIs) but not from dorsal giant interneurons (dGIs). In contrast, DUM cells that have peripheral axons consistently fail to be excited by any giant interneurons. The DUM interneurons are excited by vGIs on both sides of the CNS and, when the vGIs are excited in pairs, summation occurs. Wind fields that have been generated for two of the DUM interneurons are omnidirectional. These data, taken along with the known association of DUM cells with the neuromodulatory substance octopamine, suggest that the DUM interneurons may act to modulate central synapses.

Action Potentials↗

Modulatory effects of biogenic amines on adipokinetic hormone secretion from locust corpora cardiaca in vitro.

The control of the release of adipokinetic hormones from neurosecretory cells within the glandular lobes of the corpus cardiacum involving axons running through the paired nervus corporis cardiaci II is unclear. Cyclic-AMP (cAMP) is clearly a second messenger. The effects of four biogenic amines (octopamine, dopamine, tyramine, and serotonin) on the release of adipokinetic hormone-I were investigated in vitro. None had an effect on its own; they all potentiated the hormone release induced by cAMP-activating agents. Dopamine and serotonin were only present in the neurohemal part of the corpus cardiacum. Octopamine and tyramine were not detectable in the corpus cardiacum.

Animals↗

The metabolism of biogenic monoamines during embryogenesis and metamorphosis in two anuran species.

This study investigated the pathways to many monoamines and their metabolites in the central nervous system of the frog Rana nigromaculata and the toad Bufo bufo japonicus during embryonic development and metamorphosis. Metabolites were analyzed by three-dimensional HPLC. The two species provided evidence of similar pathways, with slightly different timetables for the development of their monoamine systems. During embryonic development, the main metabolic pathways in entire embryos were tyrosine (TYR)-->[3,4-dihydroxyphenylalanine in Bufo]-->3-hydroxytyramine-->norepinephrine or epinine (EPIN)-->epinephrine, TYR-->tyramine--> (octopamine in Rana) and TYR-->3-O-methyldopa for catecholamines, and tryptophan-->kynurenine and 5-hydroxytryptamine (5-HT)-->[5-hydroxyindoleacetic acid and N-methyl-5-hydroxytryptamine (N-MET) in Bufo]. The monoamine system in the brain was similar during metamorphosis to that during embryogenesis with a few exceptions. The most striking change was the development of the bufotenine (5-hydroxy-N, N-dimethyltryptamine) pathway from 5-HT via N-MET. EPIN and norepinephrine in Rana and octopamine in both species disappeared during metamorphosis. These results are discussed in relation to the roles of the various pathways in development.

Animals↗

The evolutionary divergence of neurotransmitter receptors and second-messenger pathways.

Members of the superfamily of G-protein-coupled neurotransmitter receptors have a conserved secondary structure, a moderate and reasonably steady rate of sequence change, and usually lack introns within the coding sequence. These properties are advantageous for evolutionary studies. The duplication and divergence of the genes in this gene family led to the formation of distinct neurotransmitter pathways and may have facilitated the evolution of complex nervous systems. I have analyzed this evolutionary divergence by quantitative multiple sequence alignment, bootstrap resampling, and statistical analysis of 49 adrenergic, muscarinic cholinergic, dopamine, and octopamine receptor sequences from 12 animal species. The results indicate that the first event to occur within this gene family was the divergence of the catecholamine receptors from the muscarinic acetylcholine receptors, which occurred prior to the divergence of the arthropod and vertebrate lineages. Subsequently, the ability to activate specific second-messenger pathways diverged independently in both the muscarinic and the catecholamine receptors. This appears to have occurred after the divergence of the arthropod and vertebrate lineages but before the divergence of the avian and mammalian lineages. However, the second-messenger pathways activated by adrenergic and dopamine receptors did not diverge independently. Rather, the ability of the catecholamine receptors to bind to specific ligands, such as epinephrine, norepinephrine, dopamine, or octopamine, was repeatedly modified in evolutionary history, and in some cases was modified after the divergence of the second-messenger pathways.

Adenylyl Cyclases↗

Amine modulation of electrical coupling in the pyloric network of the lobster stomatogastric ganglion.

1. The neurons of the pyloric network of the lobster (Panulirus interruptus) stomatogastric ganglion organize their rhythmic motor output using both chemical and electrical synapses. The 6 electrical synapses within this network help set the firing phases of the pyloric neurons during each rhythmic cycle. We examined the modulatory effects of the amines dopamine (DA), serotonin (5HT) and octopamine (Oct) on coupling at all the electrical synapses of the pyloric network. 2. Electrical coupling within the pacemaker group [anterior burster (AB) to pyloric dilator (PD), and PD-PD] was non-rectifying, while coupling at the other electrical synapses [AB to ventral dilator (VD), PD-VD, lateral pyloric (LP) to pyloric (PY), and PY-PY] was rectifying. 3. Dopamine decreased or increased the coupling strength of all the pyloric electrical synapses: the sign of the effect depended upon which neuron was the target of current injection. For example, DA decreased AB-->PD coupling (i.e., when current was injected into the AB) but increased coupling in the other direction, PD-->AB. Dopamine decreased AB to VD coupling when current was injected into either neuron. Serotonin also had mixed effects; it enhanced PD-->AB coupling but decreased AB to VD and PD to VD coupling in both directions. Octopamine's only effect was to reduce PD-->VD coupling. 4. Dopamine increased the input resistance of the AB neuron but decreased the input resistance of the PD and VD neurons. Serotonin reduced the input resistance of the VD and PY neurons, while Oct did not significantly change the input resistance of any pyloric neuron. 5. The characteristic modulation of electrical coupling by each amine may contribute to the unique motor pattern that DA, 5HT and Oct each elicit from the pyloric motor network.

Amines↗

Interaction of the pesticide chlordimeform with adrenergic receptors in mouse brain: an in vitro study.

Chlordimeform (N'(4-chloro-o-tolyl)-N, N-dimethylformamidine; CDM) is a formamidine insecticide acaricide whose major active metabolite is its N-monomethyl analog, desmethylchlordimeform, (DCDM). While their pesticidal action in invertebrates appears to be related to activation of octopamine receptors, their mechanism of action in mammals has not been established. Because of similarities between octopamine and adrenergic receptors and suggestions of CDM and DCDM action on adrenoceptors, the in vitro interactions of CDM and DCDM with adrenoceptors were studied. In mouse brain membrane preparations CDM inhibited the binding of [3H]-clonidine to alpha 2- adrenoceptors and of [3H]-WB4101 to alpha 1-adrenoceptors with IC50 values of 18.2 and 87 microM, respectively. DCDM was a much more potent inhibitor, with IC50 values toward alpha 2-, and alpha 1-adrenoceptors of 44 nM and 1 microM, respectively. Both compounds were only weak inhibitors of the binding of [3H]-dihydroalprenolol to beta-adrenoceptors and of [3H]-quinuclidinyl benzilate to muscarinic receptors and were inactive toward benzodiazepines and gamma aminobutyric acid (GABAA) receptors. Inhibition of [3H]-clonidine binding by both compounds was competitive, as indicated by a decreased receptor affinity without changes in receptor density. Interaction of CDM and DCDM with [3H]-WB4101 binding, on the other hand, was more complex, and not of the competitive type. These results show that CDM and its metabolite DCDM can interact directly in vitro with alpha-adrenergic receptors, suggesting that these receptors could mediate some of the effects of CDM and DCDM in vivo.

Amidines↗

Putative neurohemal areas in the peripheral nervous system of an insect, Gryllus bimaculatus, revealed by immunocytochemistry.

The morphology and position of putative neurohemal areas in the peripheral nervous system (ventral nerve cord and retrocerebral complex) of the cricket Gryllus bimaculatus are described. By using antisera to the amines dopamine, histamine, octopamine, and serotonin, and the neuropeptides crustacean cardioactive peptide, FMRFamide, leucokinin 1, and proctolin, an extensive system of varicose fibers has been detected throughout the nerves of all neuromeres, except for nerve 2 of the prothoracic ganglion. Immunoreactive varicose fibers occur mainly in a superficial position at the neurilemma, indicating neurosecretory storage and release of neuroactive compounds. The varicose fibers are projections from central or peripheral neurons that may extend over more than one segment. The peripheral fiber varicosities show segment-specific arrangements for each of the substances investigated. Immunoreactivity to histamine and octopamine is mainly found in the nerves of abdominal segments, whereas serotonin immunoreactivity is concentrated in subesophageal and terminal ganglion nerves. Immunoreactivity to FMRFamide and crustacean cardioactive peptide is widespread throughout all segments. Structures immunoreactive to leucokinin 1 are present in abdominal nerves, and proctolin immunostaining is found in the terminal ganglion and thoracic nerves. Codistribution of peripheral varicose fiber plexuses is regularly seen for amines and peptides, whereas the colocalization of substances in neurons has not been detected for any of the neuroactive compounds investigated. The varicose fiber system is regarded as complementary to the classical neurohemal organs.

Amines↗

Flying insects: model systems in exercise physiology.

Insect flight is the most energy-demanding exercise known. It requires very effective coupling of adenosine triphosphate (ATP) hydrolysis and regeneration in the working flight muscles. 31P nuclear magnetic resonance (NMR) spectroscopy of locust flight muscle in vivo has shown that flight causes only a small decrease in the content of ATP, whereas the free concentrations of inorganic phosphate (Pi), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) were estimated to increase by about 3-, 5- and 27-fold, respectively. These metabolites are potent activators of glycogen phosphorylase and phosphofructokinase (PFK). Activation of glycolysis by AMP and Pi is reinforced synergistically by fructose 2,6-biphosphate (F2,6P2), a very potent activator of PFK. During prolonged flight locusts gradually change from using carbohydrate to lipids as their main fuel. This requires a decrease in glycolytic flux which is brought about, at least in part, by a marked decrease in the content of F2,6P2 in flight muscle (by 80% within 15 min of flight). The synthesis of F2,6P2 in flight muscle can be stimulated by the nervous system via the biogenic amine octopamine. Octopamine and F2,6P2 seem to be part of a mechanism to control the rate of carbohydrate oxidation in flight muscle and thus function in the metabolic integration of insect flight.

Adenine Nucleotides↗

Decrease in excitability of LG following habituation of the crayfish escape reaction.

Crayfish escapes from threatening stimuli to the abdomen by tailflipping upwards and forwards. This lateral giant (LG)-mediated escape reaction habituates readily upon repetitive sensory stimulation. Using an isolated abdominal nerve cord preparation, we have analyzed the change in LG activity by applying additional sensory stimulation after different periods following habituation to characterize the retention of LG habituation. Results show that the LG mediated response habituates more quickly, but the retention time is shorter, as repetitive sensory stimulation is applied at progressively shorter inter-stimulus time intervals. The spike response of LG recovers quickly, within several minutes after habituation, but they fail to spike when an additional stimulus is applied after specific long periods following habituation. The critical period of the delay for this decrease in excitability of LG is dependent on the inter-stimulus time interval of the initial repetitive stimulus. As the inter-stimulus interval became longer, the delay needed for decrease in excitability became shorter. Furthermore, the local injection of 10(-6) mol l-1 octopamine into the neuropil just following habituation promotes the achievement of decrease in excitability. No effects were observed when 10(-6) mol l-1 serotonin and tyramine were injected. These results suggested octopamine promotes decrease in excitability of LG following habituation.

Animals↗

Brain biogenic amines and reproductive dominance in bumble bees (Bombus terrestris).

To begin to explore the role of biogenic amines in reproductive division of labor in social insects, brain levels of dopamine, serotonin, and octopamine were measured in bumble bee (Bombus terrestris) workers and queens that differ in behavioral and reproductive state. Levels of all three amines were similar for mated and virgin queens. Young workers that developed with or without a queen had similar amine levels, but in queenright colonies differences in biogenic amine levels were associated with differences in behavior and reproductive physiology. Dominant workers had significantly higher octopamine levels compared with workers of lower dominance status but of similar size, age, and ovary state. High dopamine levels were associated with the last stages of oocyte development irrespective of worker social status and behavior. These results suggest that biogenic amines are involved in behavioral and physiological aspects of regulation of reproduction in bumble bees.

Animals↗

Quantitative high-performance thin-layer chromatography of dansyl derivatives of biogenic amines.

A procedure for the separation, detection, and quantification of picomole levels of dansyl derivatives of the biogenic amines, dopamine, norepinephrine, octopamine, and serotonin, has been developed using high-performance thin-layer chromatography. The detection limit is 1 to 2 pmol. Each of the amine derivatives has been detected in insect brain tissue and a solvent system has been developed for the separation and quantification of octopamine in insect tissue samples.

Animals↗