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PubMed1991

Modification of leech behavior patterns by reserpine-induced amine depletion.

A single injection of 100 micrograms reserpine into the crop of the medicinal leech, Hirudo medicinalis, reduced CNS serotonin and dopamine levels to less than 1% of control values within 3 d. High-pressure liquid chromotography- (HPLC) determined CNS serotonin and dopamine levels remained maximally depressed for approximately 1 month following reserpine injection. Subsequently, amine levels recovered slowly, but remained depressed 6 months after reserpine injection. Following reserpine treatment, glyoxylic acid-induced fluorescence or neutral red staining closely mirrored the HPLC-determined time course of amine depletion and recovery. Acute exposure of isolated ganglia to 10 microM reserpine for periods up to 6 hr produced a 20-30% reduction of serotonin and dopamine content. The threshold concentration of reserpine necessary to produce amine depletion was approximately 1 microM. We found that reserpine treatment eliminated biting behavior within 4 d following injection. Biting behavior remained depressed below control levels for approximately 4 months, but returned to control values while CNS serotonin and dopamine levels remained significantly depressed at this time. Unexpectedly, reserpine treatment increased rather than reduced the duration of stimulus-evoked swimming activity. This behavioral change was evident within 3 d and persisted for approximately 3.5 months. To rapidly restore amine levels in reserpine-treated animals, we bathed intact leeches in pond water containing serotonin, dopamine, or octopamine. We found that biting behavior was restored following reserpine treatment by bathing intact leeches in pond water containing serotonin or dopamine, but not octopamine. Also contrary to expectations, the increase in swim duration was not reversed by bath exposure to serotonin, dopamine, octopamine, or histamine. However, all swimming activity in reserpine-treated leeches was eliminated by the amine antagonist cyproheptadine. We propose that the presence of low levels of amines is critical for the expression of both biting and swimming activity in leeches. However, the minimal levels of amines necessary for the expression of these behaviors are lower for swimming than for biting.

Animals↗
PubMed1987

Multiple mechanisms of bursting in a conditional bursting neuron.

The anterior burster (AB) neuron in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus, is a conditional burster in the pyloric motor circuit. Bath application of the monoamines dopamine, serotonin, and octopamine induces rhythmic bursting pacemaker potentials in a silent, synaptically isolated AB cell. However, each amine produces a unique and characteristic burst shape, resulting from different ionic dependences of the burst mechanisms. Bursting induced by serotonin or octopamine is critically dependent upon sodium entry through tetrodotoxin-sensitive channels; dopamine-induced bursting is not TTX-sensitive. Dopamine-induced bursting is abolished when extracellular calcium is reduced to 25% of normal; serotonin- and octopamine-induced bursts continue in this saline, although they are abolished in salines with calcium reduced to 10% or less of normal. Quantitative differences between the amines are also seen in the tetraethylammonium (TEA) sensitivity of the burst amplitude and in the dependence of the interburst hyperpolarization on extracellular potassium. These experiments demonstrate that there are both quantitative and qualitative differences in the ionic currents underlying every phase of the bursts induced by the 3 amines. Thus, a single neuron can burst via more than one ionic mechanism.

Animals↗
PubMed1977

Dopamine uptake by platelets in hepatic encephalopathy; evidence for a possible depletion of brain dopamine.

A decrease in H3-dopamine uptake was demonstrated in the blood platelets of 22 hepatic encephalopathy (HE) patients when compared to that of patients with liver cirrhosis, but without HE, and controls. There was a direct correlation between the stage of HE and the decrease in H3-dopamine uptake. As blood platelets have characteristics similar to neurons which contain amines, they have been proposed as a model for the study of amine metabolism in neurological, as well as liver diseases. A defective dopamine uptake by the HE platelets suggests that a similar biochemical derangement is, also, present in the nerve cells of the dopaminergic system. This could account for the clinical evidence of extrapiramidal dysfunction and the arousal effect of levodopa in HE. Platelets from 10 cirrhosis, but HE-free, patients had a dopamine uptake which was intermediate between the HE patients and controls. When octopamine was added at the same concentrations as in serum of HE patients, the blood platelets from five controls showed a decrease in dopamine uptake proportional to the concentration of octopamine added. Octopamine may impair dopamine uptake by platelets from HE patients.

Adult↗
PubMed2005

Isolation, cloning, and tissue expression of a putative octopamine/tyramine receptor from locust visceral muscle tissues.

Octopamine has been shown to play major roles in invertebrate nervous systems as a neurotransmitter, neuromodulator, and neurohormone. Tyramine is the biochemical precursor of octopamine and its neuromodulatory role is now being investigated and clarified in invertebrates, particularly in insects. Both octopamine and tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are believed to play important functions in the regulation of physiological processes in locust oviduct. Here we report the isolation, cloning, and tissue expression of a putative octopamine/tyramine receptor from the locust, Locusta migratoria. Degenerate oligonucleotides in PCR reactions were first used to obtain partial cDNA sequences and then these partial sequences were used in screens to obtain a full-length cDNA. The cloned cDNA is about 3.1 kb long and encodes a protein of 484 amino acid residues with typical characteristics of GPCRs including seven transmembrane domains and many signature residues. The amino acid sequence of the cloned cDNA displays sequence similarities with known GPCRs, particularly octopamine/tyramine receptors. Screening of the locust genomic DNA library resulted in isolation of a genomic DNA with the same size as the cDNA, indicating that the gene is intron-less. RT-PCR and Northern blot analyses revealed the expression of the receptor mRNA in brain, ventral nerve cord, oviduct, and midgut tissues. Southern blot analyses using EcoRI and HindIII restriction endonucleases recognized at least two distinct gene bands.

Amino Acid Sequence↗
PubMed2005

Influence of the biogenic amine tyramine on ethanol-induced behaviors in Drosophila.

The biogenic amine tyramine has been implicated in drug-induced behavior. The Drosophila inactive mutant is characterized by reduced tyramine and octopamine levels and is defective in cocaine sensitization. To test whether there is an overlap in the use of the amine neurotransmitter system in ethanol- and cocaine-induced behaviors, mutant analyses were extended to the phenotypic characterization of inactive and other mutants effecting the tyramine and octopamine neurotransmitter system. The inactive mutant displays increased ethanol sensitivity and is impaired in the initial startle response upon ethanol application. Furthermore, this mutant fails to regulate its alcohol-induced hyperactivity properly. In contrast to the defects seen after cocaine application, inactive mutants develop normal ethanol tolerance and sensitize to the locomotor activating effect of ethanol. The tyramine-beta-hydroxylase mutant (TbetaH) with increased tyramine and depleted octopamine levels displays normal ethanol sensitivity, a startle repression, and hyperactivates more in response to ethanol. In addition, TbetaH mutants fail to develop a tolerance to the hyperactivating effect of ethanol. Ethanol-induced sensitization does not seem to be impaired in either mutant, suggesting that tyramine is not required for this process. The comparative analysis of the phenotypes associated with inactive and TbetaH mutants suggests that the fine tuning of ethanol-induced hyperactivity can be correlated with different tyramine levels. Defects in other aspects of ethanol-induced behaviors might be due to different molecules or mechanisms.

Animals↗
PubMed1995

Modulation of behavior by biogenic amines and peptides in the blue crab, Callinectes sapidus.

Using the blue crab Callinectes sapidus as a model system, we have investigated the effects of potential neuromodulators on freely behaving animals. Of interest is the modulatory effect of a number of drugs on three rhythmic behaviors of the blue crab: courtship display (CD) of the male crab, sideways swimming and backward swimming. The drugs tested were proctolin, dopamine, octopamine, serotonin, and norepinephrine. Injection of each drug elicited a unique posture or combination of limb movements. These experiments showed two results pertinent to CD behavior: A posture identical to the CD posture was displayed after dopamine injection; and rhythmic leg waving similar to CD was evoked by proctolin. An unusual combination of flexion and extension of all limbs and movements of some limbs occurred after serotonin injection. Injection of octopamine led to a posture antagonistic to CD posture. The effects of these drugs were concentration- and time-dependent. Injection of dopamine, octopamine, or serotonin produced effects that were seasonally-dependent, and the influence of proctolin proved to be dependent on developmental stage. Quantitative analysis of leg waving movements after proctolin injection allowed for comparison of these movements to naturally-occurring behavior.

Aging↗
PubMed1997

The effect of neuropeptides from Limulus on its circadian rhythm in retinal sensitivity.

Retinal responses of the Limulus lateral eyes to light are greater at night than during the day. A circadian clock in the brain of the horseshoe crab controls these rhythmic changes of light sensitivity. The increase in sensitivity (as measured by the amplitude of the electroretinogram) is mediated at least in part by octopamine that is released from efferent axons terminating in the visual cells. Earlier studies indicate that certain factors in Limulus hemolymph can act in conjunction with octopamine. More recently, five neuropeptides (LP1-LP4 and Lip-HP) had been isolated from acetone extracts of the Limulus central nervous system using HPLC fractionation and radioimmunoassay with antisera against FMRFamide-like peptides for detection. Presently, we have injected into the Limulus lateral eye these five peptides and observed changes in retinal sensitivity. Injection during daytime had no immediate effect on that daytime electroretinogram but decreased the electroretinogram amplitude for the entire subsequent night (12 h). However, upon injection at night, we observed an immediate but only transitory decrease in electroretinogram amplitude for about 1 h without effect on the subsequent daytime electroretinogram. We suggest that the peptides act antagonistically to octopamine and are highly dependent upon the activity state of the efferent nerve terminals.

Animals↗
PubMed1999

Biogenic amines and division of labor in honey bee colonies: behaviorally related changes in the antennal lobes and age-related changes in the mushroom bodies.

Levels of the biogenic amines dopamine, serotonin, and octopamine were measured in different brain regions of adult worker honey bees as a function of age-related division of labor, using social manipulations to unlink age and behavioral state. In the antennal lobes, foragers had higher levels of all three amines than nurses, regardless of age. Differences were larger for octopamine than serotonin or dopamine. In the mushroom bodies, older bees had higher levels of all three amines than younger bees, regardless of behavioral state. These correlative results suggest that increases in octopamine in the antennal lobes may be particularly important in the control of age-related division of labor in honey bees.

Aging↗
PubMed1989

Semicarbazide-sensitive amine oxidase (SSAO) of the rat aorta. Interactions with some naturally occurring amines and their structural analogues.

The influence of a number of naturally occurring amines and their structural analogues has been examined on the metabolism of radiolabelled benzylamine (BZ) by the membrane bound semicarbazide-sensitive amine oxidase (SSAO) of the rat aorta. Only primary monoamines were effective in reducing the deamination of BZ. In the phenylethylamine series, addition of hydroxyl groups to the benzene ring decreased their potency as inhibitors while addition of a hydroxyl group at the beta position increased the inhibitory potency. Stereoselectivity of action was shown with octopamine, the L-isomer being the more active form. Kinetic analysis of these interactions showed predominantly competitive inhibition and kynuramine had the lowest Ki of 5.4 microM. The aliphatic monoamines, isoamylamine and isobutylamine both competed with BZ. 5-Hydroxytryptamine (5-HT) was the only amine that inhibited non-competitively. Direct evidence for metabolism by SSAO of some of the competing amines such as isoamylamine, phenylethylamine, tyramine and tryptamine was obtained by fluorimetric or radiochemical assays. The inhibitors clorgyline and (E)-2-(3',4'-dimethoxyphenyl)-3-fluoroallylamine (MDL 72145) were used to characterise the amine oxidase activity responsible for the deamination. Octopamine and phenylethanolamine (PeOH) were not SSAO substrates and inhibited BZ metabolism in the fluorimetric assay. It is possible that the activity of SSAO is controlled by octopamine released from sympathetic nerve endings or 5-HT released from platelets.

Allosteric Regulation↗
PubMed1978

Alterations in plasma and CSF amino acids, amines and metabolites in hepatic coma.

The dog with an end-to-side portacaval shunt (PCS) has been extensively used as a model to investigate hepatic encephalopathy (HE) as it demonstrates a plasma amino acid pattern similar to patients with chronic liver disease. In adult mongrel dogs, the effect of PCS on plasma and CSF amino acids, octopamine (OCT), phenylethanolamine (PEA) and CSF 5-hydroxyindolacetic acid (5-HIAA), were studied. Moreover, the effect of correction of plasma amino acids by infusional techniques was investigated.Tyrosine, tryptophan and phenylalanine levels increased dramatically during the development of HE in plasma and CSF, while valine, leucine and isoleucine decreased in plasma only, but CSF levels remained stable. Plasma and CSF octopamine and phenylethanolamine and CSF 5-HIAA increased markedly as clinical features in the dogs' behavior, characteristic of hepatic encephalopathy occurred, including hypersalivation, ataxia, flapping tremor, somnolence and finally coma. Once in coma, the dogs were infused with an amino acid mixture (F080) calculated to normalize the plasma amino acid pattern. After one to eight hours, the dogs began to awake. Simultaneously, blood, and CSF aromatic amino acids returned to their control values, as did OCT, PEA and CSF 5-HIAA. If F080 infusion was stopped, biochemical alterations would appear within one week, again accompanied by clinical hepatic encephalopathy.The results indicate that the altered levels of aromatic and branched chain amino acids, octopamine and PEA in plasma and CSF correlate well with the development of HE and that correction of the plasma amino acid abnormalities improves encephalopathy simultaneously with correction of neurotransmitter derangements in CSF.

Amines↗
PubMed1975

Discrimination of monoamine uptake by membranes of adrenal chromaffin granules.

1 The accumulation of various radioactive monoamines by isolated membranes of bovine adrenal chromaffin granules was measured by equilibrium dialysis. 2 Adenosine-5'-triphosphate (ATP) in the presence of Mg++ stimulated the uptake of all the amines tested, but the accumulation of dopamine, (-)-noradrenaline (NA), 5-hydroxytryptamine (5-HT), (plus or minus)-adrenaline and (plus or minus)-octopamine was greater than that of tyramine, (plus or minus)-metaraminol, tryptamine, beta-phenylethylamine and histamine. 3 At the higher concentration levels of the amines in the medium the ATP-dependent accumulation of dopamine, NA, adrenaline and 5-HT in the membranes reached a saturation level, whereas in the absence of the nucleotide no saturation level was attained. 4 Octopamine and 5-HT competitively inhibited the ATP-dependent uptake of NA, 5 Decrease in the incubation temperature or the presence of N-ethylameimide greatly reduced the ATP-stimulated amine accumulation. Ouabain had no effect on uptake. 6 Reserpine virtually abolished the ATP-dependent uptake of dopamine, NA and 5-HT, caused a partial inhibition of the metaraminol, octopamine and tyramine accumulation, but did not interfere with the uptake of tryptamine. 7 The content of endogenous catecholamines of the membranes was changed very little by incubation of NA and 5-HT in the presence of ATP. However, the membranes lost over 80% of their endogenous amines if incubated for 30 min without ATP. 8 The ATP content of the medium progressively decreased during the incubation of granular membranes. 9 It is concluded that the membrane of adrenal chromaffin granules discriminates between the various monoamines with regard to the magnitude of their uptake and that two mechanisms of ATP-stimulated uptake, one responsive and the other resistant to reserpine, exist at the level of this membrane. The ATP-stimulated transport at the granular membrane level may be an important factor in determining the intraneuronal storage of a physiological or false neurotransmitter.

Adenosine Triphosphate↗
PubMed1989

Second-messenger systems underlying amine and peptide actions on cardiac muscle in the horseshoe crab Limulus polyphemus.

The biochemical mechanisms by which octopamine, catecholamines and the peptide proctolin exert their actions on Limulus cardiac muscle were investigated. Amines produced long-lasting increases in the amplitude of contractions evoked by electrical stimulation. At 10(-5) mol l-1, the apparent order of potency for amine-induced increases in evoked contraction amplitude was dopamine approximately equal to octopamine greater than norepinephrine approximately equal to epinephrine. At this dose, amines produced long-lasting increases in the levels of cyclic AMP (octopamine greater than dopamine approximately equal to norepinephrine approximately equal to epinephrine), but not of cyclic GMP, in Limulus cardiac muscle. Like the amines, the adenylate cyclase activator forskolin enhanced cardiac muscle contractility and increased levels of cyclic AMP, but not of cyclic GMP. The phosphodiesterase inhibitor IBMX produced a transient increase in cardiac muscle contractility, but typically produced long-lasting negative inotropy. This agent increased levels of both cyclic AMP and cyclic GMP in Limulus cardiac muscle. Proctolin and the protein kinase C activator phorbol dB increased the contraction amplitude of the intact heart and the electrically stimulated myocardium. These compounds, as well as dopamine, elicited sustained contractures and rhythmic contractions when applied to deganglionated Limulus cardiac muscle rings. Unlike the amines, proctolin and phorbol dB did not increase cardiac muscle cyclic AMP levels. These results suggest that several second-messenger systems may be utilized by amines and peptides to produce excitatory actions on cardiac muscle fibers of the Limulus heart. Cyclic AMP appears to be an important second messenger underlying the effects of amines to enhance cardiac muscle contractility. Pharmacological data suggest that proctolin may alter cardiac muscle contractility and excitability by a mechanism which involves the phosphatidylinositol pathway. Dopamine, unlike the other amines, produces a number of proctolin-like effects and may activate both the cyclic AMP and the phosphatidylinositol systems in Limulus cardiac muscle.

1-Methyl-3-isobutylxanthine↗
PubMed1995

Octopaminergic dorsal unpaired median (DUM) neurones innervating the colleterial glands of the female cockroach Periplaneta americana

The musculature of the colleterial glands receives innervation from branch 4B4a of the nerves designated 4B, which arise from the posterior part of the terminal abdominal ganglion in the female cockroach Periplaneta americana (L). Using Methylene Blue staining, the gross anatomy of the colleterial gland innervation has been described. Cobalt backfilling via branch 4B4 of nerve 4B revealed about 21 dorsal unpaired median (DUM) neurones located on both median and posterior parts of the terminal abdominal ganglion. Octopamine immunohistochemistry has shown that at least 15 octopamine-immunoreactive DUM neurones from median and posterior groups projected via branch 4B4a to the left and right colleterial glands. These data, together with results reporting the presence of octopamine-immunoreactive branches supplying these colleterial glands, make octopaminergic DUM neurones suitable candidates to modulate the muscle activity of the colleterial glands in female Periplaneta americana.

Journal Article↗
PubMed1984

Some interrelated properties of A and B form monoamine oxidase in monkey brain mitochondria.

The multiplicity of monoamine oxidase (MAO) in monkey brain was studied by comparing the relationship between the selective substrates of MAO and the pH-activity curves obtained using these substrates. When mitochondrial and A-form MAO were used as the enzyme preparations with serotonin (5-HT) and norepinephrine (NE), preferential substrates for A-form MAO, the pH optima were 8.8 and 7.8 with 5-HT and 8.5 and 7.2 with NE. These substrates were also oxidized by B-form MAO after changing the pH of the incubation medium (shift to alkaline); these pH optima were 9.0 and 8.2, respectively. When common substrates of MAO were used (tyramine, octopamine, dopamine and tryptamine), the pH activity curves obtained were all broad and bell-shaped with pH optima for the 3 species of enzyme (mitochondria, A-form and B-form MAO) at 8.0, 7.8, and 8.0 with tyramine; 8.3, 7.5, and 8.5 with octopamine; 7.8, 7.5, and 8.5 with dopamine; and 8.0, 8.3, and 6.9 with tryptamine, respectively. The pH optima were 6.6 with beta-phenylethylamine (beta-PEA) and 9.0 with benzylamine, preferential substrates for B-form MAO, for either mitochondria or B-form MAO. The Km values obtained for tryptamine and beta-PEA were lower than those for the other substrates of MAO, regardless of the enzyme preparations. The Km and Vmax values of both forms MAO for 5-HT and NE were similar to those of the A-form MAO. The differences in the Km and Vmax values of the A-form MAO and B-form MAO for common substrates were comparable. Tyramine, octopamine and dopamine were substrates for both forms MAO, with only a slight preference for B-form MAO over A-form MAO. However, tryptamine may be deaminated predominantly by A-form MAO.

Animals↗
PubMed1986

Evidence for an ascorbate shuttle for the transfer of reducing equivalents across chromaffin granule membranes.

Adrenal chromaffin granules must shuttle reducing equivalents from the cytosol inward to reduce ascorbic acid oxidized during norepinephrine biosynthesis by intragranular dopamine-beta-hydroxylase. A transmembrane electron shuttle between the external (cytosolic) and intragranular ascorbate pools was demonstrated in vitro in intact bovine chromaffin granules undergoing tyramine- or dopamine-stimulated dopamine-beta-hydroxylase turnover. Incubation of intact chromaffin granules with tyramine results in a time-dependent decrease in reduced intragranular ascorbate and production of octopamine. The rate of ascorbate oxidation is a function of the extragranular concentrations of tyramine over the range 50 microM to 2 mM and is 95% inhibited by addition of the dopamine-beta-hydroxylase inhibitor disulfiram. The stoichiometry of octopamine synthesized/ascorbate oxidized closely approximates unity. The presence of extragranular dopamine also induces oxidation of intragranular ascorbate which is inhibited by blocking dopamine transport with reserpine. On the other hand, incubation with octopamine, which is also transported by the granules, causes no net decrease in reduced intragranular ascorbate. The presence of 400 microM extragranular ascorbate abolishes the observed tyramine-induced intragranular ascorbate oxidation. The addition of ascorbate extragranularly 30 min after addition of tyramine reverses the oxidation of intragranular ascorbate. The measurement of [14C]ascorbate distribution ratios in granule pellets and supernatants indicates that there is no transmembrane transport of ascorbate. Extravesicular NADH had no significant effect on matrix ascorbate levels during beta-hydroxylation. These data provide new in vitro evidence that chromaffin granules shuttle reducing equivalents inwardly from an extra- to an intravesicular ascorbate pool and that cytosolic ascorbate is the source of the intragranular reducing equivalents required during norepinephrine biosynthesis.

Animals↗
PubMed1984

Serotonin-induced protein phosphorylation in a lobster neuromuscular preparation.

Three substances believed to be neurohormones in the lobster--serotonin, octopamine, and proctolin--can modulate the physiology of the dactyl opener muscle of the lobster walking leg. All three act directly on muscle fibers to cause long-lasting contractures. In addition, serotonin enhances the release of transmitter from the excitatory and inhibitory axons that innervate the muscle. We now report that serotonin, applied to intact nerve-muscle preparations, increases the phosphorylation of a soluble 29,000-dalton protein by as much as 20-fold. In two respects the phosphorylation parallels the physiological effects of serotonin: both have a slow time course, and both are caused by low concentrations of serotonin (thresholds of approximately 10(-8) M). The 29,000-dalton protein is present in many lobster tissues, including thoracic ganglia, gills, and several different muscles. This suggests that the phosphorylation participates in some aspect of metabolism common to many types of cells, rather than in an activity unique to nerve or muscle. The function of the phosphorylated protein remains unknown. Several lines of evidence suggest that the phosphorylation is mediated by a cyclic nucleotide, probably cyclic AMP. (1) Adding cyclic AMP or cyclic GMP to nerve-muscle homogenates leads to the phosphorylation. (2) Adding 8-Br-cyclic AMP or 8-Br-cyclic GMP to intact preparations leads to the phosphorylation. (3) In intact tissue, forskolin, an adenylate cyclase activator, and isobutylmethylxanthine, a phosphodiesterase inhibitor, increase cyclic AMP and cyclic GMP and also cause the phosphorylation. (4) Serotonin increases cyclic AMP in intact preparations. (5) RMI 12,330A, which blocks the serotonin-induced cyclic AMP increase, also blocks the phosphorylation. (6) Serotonin has no detectable effect on cyclic GMP. This suggests that cyclic AMP, and not cyclic GMP, is the second messenger that mediates phosphorylation in vivo. In contrast, calcium is not likely to mediate the phosphorylation. Agents that block calcium channels do not block the serotonin-induced phosphorylation, and agents that increase sarcoplasmic calcium do not cause it. Furthermore, calcium does not induce the phosphorylation in a homogenate. One of the other modulators, proctolin, does not increase cyclic AMP or cause the phosphorylation even at concentrations 10(6)-fold greater than the hormone's threshold for producing contractures. The third modulator, octopamine, causes small increases in cyclic AMP and is a weak agonist of the phosphorylation. Neither proctolin nor octopamine alters cyclic GMP levels.

Animals↗
PubMed1977

Comparative study of urinary excretion rates of para-hydroxy-mandelic acid, homovanillic acid, vanylmandelic acid in cirrhotic patients with and without encephalopathy.

A comparative study of urinary excretion of octopamine, dopamine, and noradrenaline catabolic products, respectively parahydroxymandelic acid (PHMA) homovanillic acid (HVA) and vanylmandelic acid (VMA) was carried out in 27 cirrhotic patients with (11) and without (16) porto-systemic encephalopathy (P.S.E). PHMA, HVA and VMA were significantly higher in patients with PSE, and there was a positive correlation between PHMA and HVA, and between PHMA and VMA. Higher excretion of PHMA in patients with PSE strongly suggests an increased metabolism of octopamine. HVA and VMA increased excretion, and the positive correlations could be explained by the depletion of stored dopamine and noradrenaline. These observations support the hypothesis that octopamine acts as a false neurotransmitter, and the resulting depletion of dopamine and noradrenaline could explain the neuropsychic phenomena of PSE, and the awakening effect of L. Dopa treatment.

Aged↗
PubMed1997

Neuronal cAMP-dependent protein kinase type II is concentrated in mushroom bodies of Drosophila melanogaster and the honeybee Apis mellifera.

In both Drosophila melanogaster and the honeybee Apis mellifera, cyclic adenosine monophosphate (cAMP)-dependent processes have been implicated in mechanisms of learning. This study characterizes the type II cAMP-dependent protein kinase (PKAII), the major target of cAMP in adult animals. In both species, PKAII is restricted to neuronal tissue, in which it accounts for more than 90% of total PKA activity. Although the intensity of PKAII immunoreactivity differs between distinct brain regions, labeling is detectable in all neuropiles and most somata. While the visual neuropiles, the antennal lobes, and structures of the central brain exhibit intermediate immunostaining, the mushroom bodies show high labeling and contain a three- to fourfold higher PKA activity compared to other neuropiles. Since the mushroom bodies are central sites of olfactory learning mediated via cAMP-dependent signaling, the modulatory functions of transmitters on PKA activity in Kenyon cells from the honeybee were tested. Agents which elevate cytoplasmic Ca2+ levels have no effects on PKA activity in cultured Kenyon cells. Dopamine, serotonin, and octopamine, however, cause an increase in PKA activity in Kenyon cells. The modulation of PKA activity by octopamine, the putative transmitter of the unconditioned stimulus in associative olfactory learning in the honeybee, together with the findings on the central role of the cAMP cascade in Drosophila mushroom bodies, suggests a major implication of PKAII-mediated phosphorylation in learning and memory in both Drosophila and Apis.

Animals↗