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PubMed1987

Transmitter-induced glycogenolysis and gluconeogenesis in leech segmental ganglia.

1. The utilization and control of glycogen stores were studied in the isolated segmental ganglia of the horse leech, Haemopis sanguisuga. The glycogen in the ganglia was extracted and assayed fluorimetrically and its cellular localization and turnover studied by autoradiography in conjunction with [3H] glucose. 2. The glycogen levels were measured after incubation with different neurotransmitters for 60 min at 28 degrees C. The results for each experimental ganglion were compared to a paired control ganglion, and the results analysed by paired t-tests. 3. Several transmitter substances (5-HT, octopamine, dopamine, noradrenaline, histamine) produced reductions in glycogen (glycogenolysis); other transmitters (glutamate, GABA) produced increases in glycogen (gluconeogenesis); others (adenosine, glycine) produced reductions or increases, depending on concentration. Acetylcholine had no effect on the glycogen levels. 4. Most of the glycogen in the ganglia is localized in the packet glial cells, which surround the neuron perikarya. Autoradiographic analysis demonstrated that the effects of histamine and dopamine were principally on the glycogen in the glial cells. 5. Adenylate cyclase was demonstrated by electron microscope histochemistry to be localized on the plasma membranes of the glial cells, and to a lesser extent on the neuronal membranes. 6. It is concluded that the changes in glycogen in the glial cells may be party controlled by transmitters via adenylate cyclase. This may provide a sensitive mechanism for coupling neuronal activity with energy metabolism.

Animals↗
PubMed1978

Brain energy metabolism and alterations of transmitter profiles in acute hepatic coma.

Brain energy reserve, tricarboxylic cycle intermediate and some putative neurotransmitters were measured in a devascularisation model with portacaval shunt and hepatic artery ligation done in two interventions. Conditions were standardized in that physiologic parameters, i.e. body temperature, systemic arterial pressure, PO2, PCO2 and pH, were kept constant and brain tissue was obtained with the "freeze-blowing" technique designed for deep freezing brain substance in less than one second. 1. Measured values indicative of the brain energy reserve (glucose, glycogen, ATP and phosphocreatin) were not found to differ from those of sham-operated animals. 2. Of the stimulating neurotransmitters, norepinephrine, dopamine, glutamic acid and aspartic acids were reduced with the exception of acetylcholine among the inhibitory neurotransmitters GABA and cAMP were unchanged, while all others including serotonin, octopamine, and phenylethanolamine were increased. 3. The results of these experiments suggest that an inbalance of amino acids with resultant changes in neurotransmitter profiles rather than an energy deficit constitutes the factor underlying hepatic coma.

Adenosine Diphosphate↗
PubMed1988

[Neuron-neuroglia functional relation in the squid giant nerve fiber].

The present work reviews the results of a series of physiological studies carried out in the giant nerve fiber of the tropical squid Sepioteuthis sepioidea, aimed at exploring the possible involvement of different second mediators and receptor systems, in the modulation of the long-lasting hyperpolarizing response of the Schwann cell membrane potential to axonal excitation. These studies provide experimental evidence on the existence of distinct receptors for ACh, octopamine, and a VIP-like endogenous peptide in the Schwann cell plasma membrane. They also indicate that the cyclic nucleotide adenosine 3',5' monophosphate may be playing a role as second messenger for the actions of the Schwann cell nicotinic cholinergic and the octopaminergic receptors, whereas the VIP receptor may be acting through the hydrolysis of polyphosphatidylinositols. These experimental findings are discussed as evidence for the existence of a complex multistep interaction between the giant axon and its satellite glial cells, the Schwann cell.

Animals↗
PubMed1987

Physiological identification, morphological analysis, and development of identified serotonin-proctolin containing neurons in the lobster ventral nerve cord.

Amines and peptides exert a wide range of physiological actions on both central neurons and peripheral tissues. Among these actions, serotonin and octopamine are known to trigger contrasting postures when injected into freely moving lobsters. Immunocytochemical studies of lobster ganglia have identified presumptive serotonergic neurons, their central and peripheral projections, and their terminal fields of arborization. More than 100 neurons that show serotonin-like immunoreactivity have been found in the lobster nervous system (Beltz and Kravitz, 1983). From immunocytochemical studies it appears that varicosities within peripheral neurosecretory structures and endings in certain central neuropil regions arise from the same 2 pairs of large cells located in the fifth thoracic (T5) and first abdominal (A1) ganglia. Because we believed that such cells could account for the central and peripheral actions of serotonin on the postural system, we chose to study these 2 pairs of neurons in greater detail. In the previous paper, Siwicki et al. (1987) report that these neurons contain the pentapeptide proctolin in addition to serotonin. In this communication, we report that these cells can be identified reliably in living preparations; they have large fields of innervation projecting anteriorly into at least 4 segmental ganglia; these neurons are the origin of the fibers that form the thoracic second root neurosecretory regions; they are generally spontaneously active neurons that have overshooting action potentials in their cell bodies; and the serotonin and proctolin immunoreactivities are first expressed in these cells at widely different times in development.

Animals↗
PubMed1986

Mechanism-based inhibition of dopamine beta-monooxygenase by aldehydes and amides.

A mechanism for beta-chlorophenethylamine inhibition of dopamine beta-monooxygenase has been postulated in which enzyme-bound alpha-aminoacetophenone is generated, followed by an intramolecular redox reaction to yield a ketone-derived radical cation as the enzyme inhibitory species (Mangold, J. B., and Klinman, J. P. (1984) J. Biol. Chem. 259, 7772-7779). If correct, additional compounds capable of producing enzyme-bound (formula; see text) reductant should inhibit dopamine beta-monooxygenase. Phenylacetaldehyde was chosen to test this model, since beta-hydroxyphenylacetaldehyde is expected to function as a reductant in a manner analogous to alpha-aminoacetophenone. Phenylacetaldehyde exhibits the properties of a mechanism-based inhibitor. Kinetic parameters are comparable to beta-chlorophenethylamine under both initial velocity and inactivation conditions. Since phenylacetaldehyde bears little resemblance to beta-chlorophenethylamine, its analogous inhibitory action provides support for an intramolecular redox reaction (via beta-hydroxyphenylacetaldehyde oxidation to a radical cation) in dopamine beta-monooxygenase inactivation. beta-Hydroxyphenylacetaldehyde was identified as the enzymatic product of phenylacetaldehyde turnover. As predicted, this product behaves both as a time-dependent inhibitor of dopamine beta-monooxygenase and as an electron donor in enzyme-catalyzed hydroxylation of tyramine to octopamine. Phenylacetamide and p-hydroxyphenylacetamide are also found to be mechanism-based inhibitors of dopamine beta-monooxygenase. In this case the product of hydroxylation (beta-hydroxyphenylacetamide) is redox inactive and, therefore, is unable to function as either a reductant or an inhibitor. Thus, mechanism-based inhibitors are divided into two types: type I, which undergoes hydroxylation prior to inactivation, and type II, which only requires hydrogen atom abstraction. A general mechanism for dopamine beta-monooxygenase inactivation is described, in which a common mechanistic radical intermediate is formed from both pathways.

Adrenal Medulla↗
PubMed1985

[Dopamine-stimulated glycosylation of rat hippocampal proteins in vitro: structure-response relationship].

Dopamine, but also other catecholamines (noradrenaline, adrenaline and isoprenaline), as well as L-dopa and alpha-methyl-dopa increase the incorporation of L-[1-3H]fucose into proteins of rat hippocampal slices. Among all substances that have been tested, dopamine exhibited the highest activity. Other non- or monohydroxylated phenylethylamine-derivatives (tyramine, octopamine, beta-phenylethylamine, metamphetamine) and pyrogallol had no effect on the fucosylation of hippocampal proteins. alpha-Methyl-dopa was less active than L-dopa. However, under the influence of alpha-methyl-dopa, an inhibitor of the dopadecarboxylase (aromatic L-amino acid decarboxylase, EC 4.1.1.28) the stimulatory effect of L-dopa on protein fucosylation was attenuated. From these results it is concluded that the dopamine-stimulated glycosylation of hippocampal proteins is triggered by (at least) two mechanisms, i.e. (1) via an activation of adenylate cyclase coupled dopamine receptor sites, and (2) via a mechanism which appears to be not related to an activation of transmitter-receptor sites but linked to the 3,4-dihydroxy-phenylethylamine-structure.

Animals↗
PubMed1981

Effects of maternal ethanol consumption of neurotransmitters and lipids in offspring.

The effects of maternal alcohol consumption on the levels and metabolism of neurotransmitters in offspring are reviewed. In addition, studies of CNS myelination and hepatic lipids are discussed. In utero exposure to ethanol is reported to alter the steady-state levels, metabolism or release of catecholamines, octopamine, serotonin, glutamate, GABA, acetylcholine and histamine. However, with the exception of a deficit of hypothalamic norepinephrine and a deficit of whole brain serotonin, most of the neurotransmitter alterations appear to be either transient or were detected when ethanol was present in the fetus or neonatal animals. There are conflicting reports on the effect of pre- and early postnatal exposure to ethanol on CNS myelination in the rat. However, it appears that if ethanol and control rats were of comparable body weights, there were only minor differences in myelination. Nonetheless, if the rat mothers consumed ethanol for 1 1/2--2 months prior to conception and during gestation, the offspring had increased myelin early in development. An examination of hepatic lipids in the fetal and neonatal rats that were exposed to ethanol in utero and at the time of sacrifice demonstrated an increased concentration of hepatic lipids and decreased fatty acid oxidation. The discussion of the neurotransmitter, myelin and hepatic lipid studies include an assessment of the nutritional status of the animals and the permanence of any observed abnormalities.

Alcohol Drinking↗
PubMed1982

Synthesis an accumulation of putative neurotransmitters by cultured neural crest cells.

The events mediating the differentiation of embryonic neural crest cells into several types of neurons are incompletely understood. In order to probe one aspect of this differentiation, we have examined the capacity of cultured quail trunk neural crest cells to synthesize, from radioactive precursors, and store several putative neurotransmitter compounds. These neural crest cultures develop the capacity to synthesize and accumulate acetylcholine and the catecholamines norepinephrine and dopamine. In contrast, detectable but relatively little synthesis and accumulation of 5-hydroxytryptamine gamma-aminobutyric acid, or octopamine from the appropriate radiolabeled precursors were observed. The capacity for synthesis and accumulation of radiolabeled acetylcholine and catecholamines is very low or absent at 2 days in vitro. Between 3 and 7 days in vitro, there is a marked rise in both catecholamine and acetylcholine accumulation in the cultures. These findings suggest that, under the particular conditions used in these experiments, the development of neurotransmitter biosynthesis in trunk neural crest cells ijs restricted and resembles, at least partially, the pattern observed in vivo. The development of this capacity to synthesize and store radiolabeled acetylcholine and catecholamines from the appropriate radioactive precursors coincides closely with the development of the activities of the synthetic enzymes choline acetyltransferase and dopamine beta-hydroxylase reported by others.

Acetylcholine↗
PubMed1981

Clinical application of the probenecid test for measurement of monoamine turnover in the CNS.

The probenecid-induced accumulation of the acidic metabolites of dopamine and serotonin is widely used to estimate the CNS turnover of these amines in human subjects. The theoretical basis of the probenecid test is discussed, including the assumptions on which the test is based, and the limitations of the procedure. Suggestions are offered on appropriate methods for analyzing test data. Available evidence suggests that maximal inhibition of the efflux of the acidic metabolites of dopamine and serotonin from the CSF is not achieved with probenecid doses up to 100 mg/kg. Therefore, before a comparison can be made between the accumulation of CSF metabolites from different groups of subjects, a correction for CSF probenecid concentrations is necessary. Moreover, in addition to the measurement of dopamine and serotonin turnover, the probenecid test can be extended to include comparisons of CNS turnover of other monoamines including octopamine, p-tyramine, and tryptamine.

Brain↗
PubMed1984

Vasoactive factors in decompensated cirrhosis. Effect of acute plasma expansion.

Plasma volume expansion was performed in 16 cirrhotic patients with ascites, 8 with avid sodium retention (sodium retainers) and 8 with normal sodium balance (sodium excretors). No natriuretic response was observed in sodium retainers (daily UNa = 7.1 +/- 1.5 mEq before expansion and 20.8 +/- 7.8 after expansion; p = not significant). After expansion plasma renin activity and plasma aldosterone showed a fall in both groups, whereas urinary kallikrein excretion decreased significantly in sodium retainers (27.1 +/- 9.7 before expansion and 7.8 +/- 6.4 after expansion; p less than 0.05). Baseline PGE were higher than normal in sodium retainers (997.0 +/- 134.3; p less than 0.02 vs. controls) and increased after expansion. Plasma octopamine was always within normal range. These results suggest that: a) reduction of effective plasma volume is not the main factor involved in sodium retention; b) the renin-angiotensin-aldosterone system has only a permissive role; c) prostaglandin system is activated and could have a protective role in maintaining renal function in cirrhotic patients.

Adult↗
PubMed1978

High-performance liquid-chromatographic separation and fluorescence measurement of biogenic amines in plasma, urine, and tissue.

We describe a high-performance liquid-chromatographic method for measuring histamine, norepinephrine, octopamine, normetanephrine, dopamine, serotonin, and tyramine in plasma (2 ml), brain (0.2 g), or urine. These amines are modifed by pre-column derivatization with o-phthalaldehyde, which stabilizes the molecules, facilitates extraction, and improves detection of nanogram amounts. Before separation, samples were neutralized with KOH and immediately derivatized and extracted into ethyl acetate, in which derivatives were stable for longer than 24 h. Interfering amino acids were removed from ethyl acetate by partitioning twice with Na2HPO4 buffer (pH 10.0). Separation was complete in about 90 min on a ""mu Bondapak/phenyl" column, with which a stepwise gradient of methanol/phosphate buffer (pH 5.1) was used. A variable-wavelength fluorometer was used (exciting wavelength, 340 nm; emission wavelength, 480 nm). Amount and response were linearly related from 1 to 200 pmol. Precision (CV) for retention times was 1%, for derivatization and injection 2.5%. Analytical recoveries of the seven amines from 2 ml of plasma fortified with 200 pmol averaged 65% (CV approximately 8%). Data on rat-brain tissue samples are compared with results by the trihydroxyindole method. Application of the method to urine from normal persons and a patient with a brain tumor is demonstrated.

Biogenic Amines↗
PubMed1981

[On the neuro-psychiatric symptomatology of the so-called "hepatic coma" (author's transl)].

The definition of hepatic coma has been used for the most severe course of hepatic insufficiency, independent from the pathogenesis. This means, that from the psychiatric point of view the hole survey of the exogen reaction type was subdivided. The neurologic symptomatology was rather neglected. In this study an attempt is made to show--using the reports of 77 patients with severe hepatic insufficiency of different etiology--that with very exact and repeated examinations a typical course of neuro-psychiatric symptoms can be observed. A distinct hierarchy of symptoms is existing, which is similar to the well known princip of dissolution (Jackson). As a main factor one has to differentiate between an acute and a subacute course. The acute course is characterized by a rapid decrease of vigilance and increase of neurologic symptoms, which end in most of the cases with an acute midbrain- and bulbarbrain-syndrome, while the subacute course shows primary a disturbance of thymo- and noopsychic function in different relations. In addition to the organic "Achsensyndrom" amnestic or amentiell symptoms can be found, which might be covered by a decrease of the vigilance--if the primary noxis continoues--end up with unconsciousness. The parallel developing neurologic symptomatology shows a distraction of the general motoric, including so-called basic movements. later stereotypies and automatismes, and the delicate distal movements change into rough general-rotation-and pointing movements of the hole body. There is also a temporary bending of all extremities and at this time also a rigidospasticity. In the following course preponderate transient bending or stretching, finally there exists a lack condition, which does not respond to external provocations. The symptomatology is not always symmetric. Transient or longstanding hemiparetic symptoms and also crossed brainstem symptoms can be seen frequently. Sometimes there are general or focal epileptic seizures. If a brain edema occurs it leads to a tentorial herniation with the symptoms of an acute midbrain- or bulbarbrain syndrome, which exists in nearly every second patient. If the course turns, the clinical symptomatology is passed in reverse direction. A good relation exists to the known biochemical changes. The disturbed monoaminmetabolism influences the structures, which are important for the vigilance. The serotonin and 5-hydroxyindolaminoacid level in the tegmentum and the hippocampus are increased. Worth to mention, that this is not a specific hepatic disturbance. Additional one can find false transmitters, for example octopamin, which are concerning the excitation, less potent than dopamin or noradrenalin and also a decrease of the latter in the extrapyramidal structures, which corresponds very well with the motoric deficiency and defectsymptoms. Not all of the symptoms can be explained by disturbances of the catecholaminmetabolism. It seems, that electrolyt and acid-base disturbances are also of some value...

Acetoin↗
PubMed1982

Blood-brain barrier derangement in uremic encephalopathy.

A disturbance of cerebral neurotransmitters and an accumulation of octopamine, a putative false neurotransmitter, have been found in patients with uremic encephalopathy who manifest disorientation, somnolence, asterixis, and coma--symptoms also seen in portal systemic encephalopathy (PSE). Altered plasma concentrations of the neutral amino acids (NAAs) and increased blood-brain NAA transport may play a role in PSE, and in the present study plasma amino acid concentrations and blood-brain barrier NAA transport were investigated in rats with acute and chronic uremia. Acute uremia was produced by unilateral nephrectomy and occlusion of the renal artery of the remaining kidney for 70 minutes; the animals were studied 24 hours later. Chronic uremia was produced by unilateral nephrectomy and 70% to 80% devascularization of the remaining kidney; these animals were studied 2 weeks later. Brain uptake was studied with the technique of Oldendorf, and blood and brain amino acids (AAs) were measured. The blood urea nitrogen (BUN) level in rats with acute uremia increased to 108 mg/dl, in rats with chronic uremic 54 mg/dl, and in sham-operated rats 22 mg/dl. In both uremic groups there was a decrease in plasma branched-chain AAs. In the brain these AA levels were normal, while levels of phenylalanine, tyrosine, and histidine were increased in uremic rats.

Amino Acids↗
PubMed1981

Evidence for a D1 dopamine receptor in the salivary glands of Amblyomma americanum (L.).

Adenylate cyclase from the salivary gland of the lone star tick, Amblyomma americanum, is stimulated by several derivatives of phenylethylamine; dopamine, noradrenaline, adrenaline and isoproterenol. Octopamine and iota-DOPA had no effect on basal adenylate cyclase activity. Dopamine had the highest potency and the lowest Ka, 0.4 micron; followed by adrenaline and noradrenaline, 23 micron; and isoproterenol, 0.15mM. When either noradrenaline or adrenaline was added to dopamine, each at its maximally effective concentration, no additional stimulation of gland cyclase activity was noted. Furthermore, adrenaline and noradrenaline together did not equal the potency of dopamine alone. The most potent inhibitors of gland cyclase activity were the dopamine receptor antagonists. The phenothiazine drugs (thioridazine, chlorpromazine, and fluphenazine) were more effective inhibitors of cyclase activity than the butyrophenone drug (haloperidol). The inhibition constants (Ki) for the phenothiazine drugs were: 60nM for thioridazine, 1.9 micron for chlorpromazine and 2.3 micron for fluphenazine. The inhibition of adenylate cyclase activity was found to be specific for the (+) enantiomer of butaclamol, a stereospecific dopamine receptor antagonist. Our findings suggest that the lone star tick salivary gland adenylate cyclase has a D1 type dopamine receptor.

Adenylyl Cyclases↗
PubMedDate not supplied

Selective amono acid solutions in hepatic encephalopathy treatment (a preliminary report).

Hepatic encephalopathy may complicate chronic liver diseases and portosystemic shunting. Recently it has been suggested that a change in the blood amino acid pattern (with elevated phenylalanine, tyrosine, methionine and depressed branched chain amino acids) and increased levels of octopamine and phenylethanolamine (a false neurotransmitter) are related causally to neurological symptoms. Previous works have suggested that an amino acid mixture of special formulation (enriched in branched chain amino acids and poor in aromatic amino acids) can normalize the plasma amino acid levels and consequently improve the neurological state. In order to test the actual therapeutic effect of these specially formulated solutions, the following therapeutic protocols were administered to 3 groups of cirrhotic patients: group 1 (15 cases): lactulose; group 2 (8 cases): special amino acid solutions; group 3 (8 cases): special amino acid solutions and lactulose. Clinical, laboratory and EEG examinations in a preliminary experiment, before and after treatment, showed that the best effect was obtained by the combined treatment with amino acid solutions and lactulose.

Adult↗
PubMedDate not supplied

Neuropharmacological studies on identified central neurones of the snail, Helix aspersa.

Central neurones of the snail, Helix aspersa, possess both synaptic and somatic receptors to a wide range of classical transmitters and neuroactive peptides. The range of receptors and the type of response is reasonably constant for a specific neurone. This review will provide data concerning the pharmacology of acetylcholine, serotonin, dopamine, noradrenaline, octopamine, glutamate, GABA and purine receptors on identified neurones. Many of these neurones also respond to neuroactive peptides including molluscan peptides, e g, AMPMLRLamide, LSSFVRIamide, SGQSWRQGRPFamide, FMRFamide; coelenterate peptides, e g, pQGRFamide; echinoderm peptides, e g, GFNSALMFamide; and nematode peptides, e g, KNEFIRFamide, KHEYLRFamide, SDPNFLRFamide. Using this data, the pharmacological profiles of identified neurones will be summarised.

Animals↗
PubMed1996

Cloning and functional characterization of a novel dopamine receptor from Drosophila melanogaster.

A cDNA clone is described that encodes a novel G-protein-coupled dopamine receptor (DopR99B) expressed in Drosophila heads. The DopR99B receptor maps to 99B3-5, close to the position of the octopamine/tyramine receptor gene at 99A10-B1, suggesting that the two may be related through a gene duplication. Agonist stimulation of DopR99B receptors expressed in Xenopus oocytes increased intracellular Ca2+ levels monitored as changes in an endogenous inward Ca2+-dependent chloride current. In addition to initiating this intracellular Ca2+ signal, stimulation of DopR99B increased cAMP levels. The rank order of potency of agonists in stimulating the chloride current is: dopamine > norepinephrine > epinephrine > tyramine. Octopamine and 5-hydroxytryptamine are not active (< 100 microM). This pharmacological profile plus the second-messenger coupling pattern suggest that the DopR99B receptor is a D1-like dopamine receptor. However, the hydrophobic core region of the DopR99B receptor shows almost equal amino acid sequence identity (40-48%) with vertebrate serotonergic, alpha 1- and beta-adrenergic, and D1-like and D2-like dopaminergic receptors. Thus, this Drosophila receptor defines a novel structural class of dopamine receptors. Because DopR99B is the second dopamine receptor cloned from Drosophila, this work establishes dopamine receptor diversity in a system amenable to genetic dissection.

Amino Acid Sequence↗
PubMed1995

The role of proctolin in the antenna-heart beat acceleration of Periplaneta americana (L.).

So-called accessorial pulsatile circulatory organs in insects have developed during evolutionary reduction of the vascular system. As such a peripheral organ, the antenna-heart supplies the antennae with haemolymph. In the antenna-heart, the beat rhythm is generated by a myogenic automatism and is controlled neuronally. The electrical stimulation of the antenna-heart nerve produces an immediate heart beat inhibition brought about by octopamine release. Following this heart inhibition, an accelerating effect can be observed, which is based on a peptidergic mechanism. Proctolin-like material was found in both the dilator muscle and the antenna-heart nerve by means of immunocytochemistry. After HPLC-separation of antenna-heart tissue, proctolin was identified by sequencing the bioactive material and subsequent mass spectrometry. Proctolin proved to be extraordinarily effective producing stimulation of the antenna-heart beat rate up to 450%. The threshold concentration is 10(-10) mol.1(-1) and the value of the dissociation constant was fixed to KO = 1.3 x 10(-8) mol.1(-1). The chrono-trophic effect is caused by an increase in the steepness of the rising phase of pacemaker activity. The enhancement of the membrane resistance Rinput indicates a reduction of K(+)-conductance by proctolin. The PI-second messenger system is involved as well. Proctolin was identified and isolated from a real target organ. This fact and the physiological results furnished proof of peptidergic transmitter function of proctolin in the antenna-heart.

Animals↗