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PubMed1978

Cellular accumulation of amines and amino acids in the central ganglia of a gastropod mollusc, Planorbis corneus: an autoradiographic study.

The distribution of radioactivity was examined autoradiographically in ganglia exposed to 10 different tritium-labelled compounds, some putative transmitters and the others transmitter precursors. The autoradiographic pattern was found to vary greatly for different substances, suggesting the presence of several different accumulating systems in the ganglia. Identified amine-containing neurons take up their own transmitter substance specifically. However, whereas uptake by dopamine-containing, and presumed histamine-containing neurons occurs over both perikarya and processes, in 5-HT-containing neurons it appears restricted to axon processes. The transmitter precursors L-DOPA and 5-hydroxytryptophan were taken up by the perikarya of both dopamine- and 5-HT-containing neurons, possibly by the same uptake system. In high concentrations, tyramine was selectively accumulated by cells containing dopamine and by non-dopamine (possibly octopamine- or tyramine-containing) neurons, but in low concentrations it labelled only the latter. GABA labelled a separate population of neurons and was particularly concentrated in their processes. Some, if not all, of the neurons specifically labelled after exposure to glutamic acid are neurosecretory cells. Tyrosine and glycine appeared to be accumulated in a non-specific manner and many of the substances were also accumulated by glial cells or by parts of the connective tissue capsule.

5-Hydroxytryptophan↗
PubMed1975

The nature of inhibition of cat brain mitochondrial monoamine oxidase by clorgyline.

In the cat brain the highest monoamine oxidase (MAO) activity is observed in the hypothalamus followed by hippocampus, caudate nucleus, pons and median cortex. Tyramine was the most actively deaminated substrate tested followed by dopamine. Clorgyline was more selective in its inhibitory action and could distinguish between tyramine and dopamine MAO deaminating system. The latter being more resistant to inhibition. The multiple forms of solubilized MAO as separated by polyacrylamide gel electrophoresis have varying phospholipid phosphorus content and sensitivity to inhibition by clorgyline in vitro and in vivo.

Animals↗
PubMed1983

Chronic haloperidol and adrenergic receptor sensitivity in the rat.

Rats were administered haloperidol (3-4 mg/kg/day) in their drinking water for 42 days, and experiments conducted on the seventh day of withdrawal. Anaesthetized haloperidol treated rats exhibited a similar mean blood pressure (BP) and heart rate (HR) response to control rats when challenged with phenylephrine (IV). When similarly pretreated rats were challenged with one of four possible doses of clonidine (IV), haloperidol treated rats were less sensitive than control rats to clonidine's hypertensive action, but there were no effects of treatment on the hypotensive (BP) effect of clonidine nor on its bradycardic effect. When one of six possible doses of tyramine was administered a similar mean BP response was seen in both treatment groups, but the positive HR response in the haloperidol-treated group was much less than in the vehicle-treated group. Atria isolated from haloperidol treated or control rats revealed a similar chronotropic response to noradrenaline and tyramine challenge. These data indicate that chronic haloperidol does not cause a generalized change in alpha-adrenergic receptor sensitivity. Nevertheless, it is clear that haloperidol has produced changes in the cardiovascular response of rats to these drugs.

Animals↗
PubMed1975

[Circulatory reflexes in primary aldosteronism (author's transl)].

1. In 7 patients with hypertension, aldosteronism, and low plasma renin (6 patients with a solitary adrenal adenoma, 1 patient with bilateral adrenal hyperplasia) circulatory reflexes (Valsalva's maneuver, head-up tilt and cold pressure test) were examined. Furthermore, the reactivity to the pressor action of tyramine and norepinephrine was determined. For comparison 10 patients with essential hypertension were studied. 2. In 4 of the 7 patients with primary aldosteronism no overshoot following Valsalva's maneuver could be observed. Compared to the patients with essential hypertension the mean overshoot in the patients with primary aldosteronism was significantly reduced. The decrease in blood pressure during head-up tilt was significantly more pronounced in the patients with primary aldosteronism. However, both groups did not differ in their reaction to the cold pressure test. In the patients with primary aldosteronism responsiveness to tyramine was significantly reduced compared to the patients with essential hypertension. No significant difference was observed in the reactivity to norepinephrine between both groups studied. 3. The results point towards a disturbance of the sympathetic nervous system in patients with primary aldosteronism.

Adult↗
PubMed1976

[Specific and non-specific effects of beta-adreno-receptor blocking drugs in man (author's transl)].

The effect of tyramine infusion or exercise on catecholamine concentration and dopamine-beta-hydroxylase activity in plasma of normal volunteers has been studied. Whereas the increase in plasma catecholamine concentrations by tyramine infusion was not changed 90 min after oral application of a single dose of beta-adrenoceptor blocking drugs (penbutolol, practolol, I.C.I. 66082), the increase in blood pressure was diminished. However, the increase in plasma catecholamine, concentration, i.e. the adrenergic response to exercise was significantly enhanced during beta-adrenoceptor blockade. On the other hand, dopamine-beta-hydroxylase activity was not further increased during beta-adrenoceptor blockade. - The non-specific membrane activity of the beta-adrenoceptor blocking drugs wass assessed by the degree of inhibition of serotonin uptake by human platelets in vitro. Their order of potency, according to IC 50 values estimated from the dose response curves was: propranolol less than penbutolol less than practolol less than I.C.I. 66082. The inhibitory activity of these drugs in vivo was also studied by measuring serotonin uptake by platelets isolated 90 min after oral administration. Due to the high dose only propranolol showed a marked membrane activity.

Adrenergic beta-Antagonists↗
PubMed1978

[In vitro biosynthesis of octopamine by the nervous system and the heart of the mollusc gastropode Helix pomatia (author's transl)].

The tyrosine is decarboxylated in vitro by the central nervous tissue and by the intracardiac nervous tissue of Helix pomatia by aromatic amino-acid decarboxylase. The tyramine obtained is then partially transformed into octopamine by tyramine-beta-hydroxylase. The inhibition of monoamine oxidase favours apparition of the 2 amines. The monoamine oxidase seems able to regulate their synthese and to assure their inactivation.

Dopamine beta-Hydroxylase↗
PubMed1992

Biochemical effects of high single doses of moclobemide in man: correlation with plasma concentrations.

The effects of high single doses of moclobemide (300, 450 and 600 mg given at the end of a standardized meal) on plasma levels of several catecholamines and their deaminated metabolites, and on plasma levels of pituitary hormones were determined in eight healthy young male volunteers in a randomized, double-blind, placebo-controlled study. Assessment of the i.v. tyramine potentiation and determination of the plasma levels of moclobemide were also performed. The tyramine sensitivity factor at 2 h after dosing was about 2.1, with no significant differences between the doses used. The inhibitory activity of moclobemide on MAO-A was reflected in significant reductions of plasma concentrations of DHPG and 5-HIAA. No clear differences were detected between the moclobemide doses. Prolactin plasma concentrations were only slightly increased after the two higher doses. The plasma concentrations of moclobemide were very much in agreement with those found in previous studies under similar experimental conditions. Thus, single oral doses of 300, 450 and 600 mg moclobemide demonstrated marked inhibition of MAO-A activity, whereas a single dose of 300 mg induced a near-maximum effect.

Adult↗
PubMed2003

Inhibitory effect of trans-N-p-coumaroyl tryamine from the twigs of Celtis chinensis on the acetylcholinesterase.

The methanolic extract of the twigs of Celtis chinensis was found to show inhibitory activity on acetylcholinesterase (AChE), an enzyme that plays a role in the metabolic hydrolysis of ACh. Bioassay-guided fractionation of the methanolic extract resulted in the isolation of N-p-coumaroyl tyramine, as an inhibitor on AChE. This compound inhibited AChE activity in a dose-dependent manner, and the IC50 value of trans-N-p-coumaroyl tyramine was 34.5 microg/mL (122 microM).

Acetylcholine↗
PubMed2001

Nitric oxide induces hydroxyl radical generation in rat hearts via depolarization-induced nitric oxide synthase activation.

We examined the effect of NG-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, on extracellular potassium ion concentration ([K+]o) and induced hydroxyl free radical (.OH) generation by an in vivo microdialysis technique. A flexibly mounted microdialysis technique was used to detect the generation of .OH in in-vivo rat hearts. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rats and tissue was perfused with Ringer's solution through the microdialysis probe at a rate of 1.0 microl/min. To measure the level of .OH, sodium salicylate in Ringer's solution (0.5 nmol/microl per min) was infused directly through a microdialysis probe to detect the generation of .OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (2,3-DHBA). Induction of high-concentration [K+]o (20, 70 and 140 mM) significantly increased formation of .OH trapped as 2,3-DHBA in a concentration-dependent manner. However, the application of L-NAME (50 mg/kg, i.v.) and allopurinol, a xanthine oxidase inhibitor, abolished the [K+]o depolarization-induced .OH generation. Tyramine (1.0 mM) increased the level of 2,3-DHBA. However, the application of L-NAME did not change the level of 2,3-DHBA. On the other hand, pretreatment with allopurinol (10 mg/kg, i.v.) abolished the KCl- or tyramine-induced .OH generation. Moreover, when iron (II) was administered to [K+]o (70 mM)-pretreated animals, there was a marked increased in the level of 2,3-DHBA. However, the application of L-NAME was not related to a Fenton-type reaction via [K+]o depolarization-induced .OH generation. To examine the effect of L-NAME on ischemic/reperfused rat myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion by left anterior descending coronary artery branch (LAD). When the heart was reperfused, a marked elevation of the level of 2,3-DHBA was observed. However, L-NAME attenuated .OH generation by ischemic/reperfused rat heart. These results suggest that NOS inhibition is associated with a cardioprotective effect due to the suppression of [K+]o depolarization-induced .OH generation.

Allopurinol↗
PubMed2001

Octopamine influences division of labor in honey bee colonies.

Forager honey bees have higher brain levels of octopamine than do bees tending larvae in the hive. To test the hypothesis that octopamine influences honey bee division of labor we treated bees orally with octopamine or its immediate precursor tyramine and determined whether these treatments increased the probability of initiating foraging. Octopamine treatment significantly elevated levels of octopamine in the brain and caused a significant dose-dependent increase in the number of new foragers. This effect was seen for precocious foragers in single-cohort colonies and foragers in larger colonies with more typical age demographies. Tyramine treatment did not increase the number of new foragers, suggesting that octopamine was exerting a specific effect. Octopamine treatment was effective only when given to bees old enough to forage, i.e., older than 4 days of age. Treatment when bees were 1-3 days of age did not cause a significant increase in the number of new foragers when the bees reached the minimal foraging age. These results demonstrate that octopamine influences division of labor in honey bee colonies. We speculate that octopamine is acting in this context as a neuromodulator.

Adrenergic alpha-Agonists↗
PubMed2000

Uptake and degradation of radioactively labelled albumin microspheres as markers for Kupffer cell phagocytosis.

Rats were injected with liposomes containing iodixanol (CTP10 Injection; 100 mg iodine per kg body weight) followed by a second injection of 125I-tyramine-cellobiose-albumin microspheres. The amounts of phagocytosed and degraded labelled albumin in liver were measured. A reduced uptake and degradation of albumin microspheres was observed when the labelled microspheres were injected 2 h or 24 h after the liposomes compared with that obtained in control animals receiving saline. No effect on the uptake and degradation of labelled microspheres was observed when the time lag between the injection of liposomes and labelled microspheres was 1 week. The data show that the uptake and degradation of 125I-tyramine-cellobiose-albumin microspheres can be used as indicators of Kupffer cell phagocytotic function following drug uptake by these cells.

Albumins↗
PubMed2003

Reactivity study on microperoxidase-8.

The catalytic activity of the microperoxidase-8/H(2)O(2) system toward tyramine and 3-(4-hydroxyphenyl)propionic acid has been determined in acetate buffer, pH 5.0. Operating with a strong excess of hydrogen peroxide, the rate-determining step of the reaction was substrate oxidation. Owing to the fast microperoxidase-8 degradation, only the very initial phase of the reactions were analyzed. The reaction rates follow a substrate saturation behavior, with turnover numbers [ k(cat)=26+/-1 s(-1) for 3-(4-hydroxyphenyl)propionic acid and k(cat)=22+/-1 s(-1) for tyramine] that were similar for the two substrates. In contrast, the K(M) values indicated a reduced affinity for the catalyst active species by the positively charged phenol, probably due to repulsive interaction with the protonated N-terminal microperoxidase-8 amino group. The reactivity of the catalyst active species was studied upon incubation of microperoxidase-8 with a small excess hydrogen peroxide, followed by reaction with the phenolic substrates. The kinetic analysis showed that more than two active species are accumulated. The species responsible for the faster reactions was present in solution as a minor fraction. The active intermediate which accumulated in a larger amount (intermediate III) has a reduced substrate oxidation activity. Comparison of this activity with the kinetic constants obtained under turnover experiments shows that intermediate III is not involved in the microperoxidase-8 catalytic cycle. The active species of the catalytic process are intermediates I and II, which in the absence of substrate rapidly convert to intermediate III.

Animals↗
PubMed1985

Measurement of plasma pyridoxal 5'-phosphate by combination of an enzymatic assay with high-performance liquid chromatography/electrochemistry.

An assay method for the determination of pyridoxal 5'-phosphate (PLP) in plasma is presented. The procedure is rapid and requires only a small volume. The method includes PLP-dependent enzymatic decarboxylation of L-tyrosine to tyramine (enzyme used: L-tyrosine apodecarboxylase (EC 4.1.1.25) from Streptococcus faecalis) and measurement of tyramine by high-performance liquid chromatography with electrochemical detection. This technique confers specificity, rapidity, and low-cost measurement. Human plasma PLP from 30 normal healthy adults had a mean value of 65.10 +/- 4.70 nM. Sensitivity of the reaction was 1.3 nM and the coefficient of variation of the method (30 repeated assays of sample with a value of 60 nM) was 1.9%.

Adult↗
PubMed1985

125I-glycoconjugate labels for identifying sites of protein catabolism in vivo: effect of structure and chemistry of coupling to protein on label entrapment in cells after protein degradation.

Residualizing radioactive labels are designed to remain entrapped within cells following degradation of a carrier protein, and have been used for identification of the tissue and cellular sites of plasma protein catabolism. In this study we describe a convenient synthesis and purification of a series of 125I-labeled glycoconjugates, and an evaluation of their efficiency of retention in liver following degradation of a model carrier protein, asialofetuin. Glycoconjugates were prepared in 65-90% yield by reductive amination of reducing sugars with aromatic amines using NaBH3CN. The products were purified in a single ion-exchange chromatographic step, and then labeled with 125I. The derivatives prepared were mono-and disubstituted lactitol-,cellobiitol-and glucitol-[125I]tyramine and lactitol-[125I]tyrosine. 125I-Glycoconjugates were coupled to asialofetuin using either cyanuric chloride or, for lactose-containing labels, by treatment with galactose oxidase followed by reductive amination with NaBH3CN. Attachment of labels by either procedure did not affect the normal rapid clearance of asialofetuin from the rat circulation nor its uptake and degradation in liver lysosomes. Leakage of 125I-labeled degradation products from cells was measured by following the kinetics of loss of whole-body radioactivity. We observed that degradation products from larger, disubstituted glycoconjugates were retained more efficiently than those from smaller and monosubstituted derivatives, and that glycoconjugates coupled to protein via reductive amination were retained in the body more efficiently than those coupled by cyanuric chloride. Overall, dilactitol-[125I]tyramine coupled to protein by reductive amination was entrapped most efficiently in liver.

Animals↗
PubMed1982

Functional distinction between serotonin uptake and serotonin-induced shape change receptors in rat platelets.

Tyramine and dopamine are taken up by rat platelets through the serotonin uptake mechanism while phenethylamine is not taken up. This indicates that an aromatic hydroxyl group is a structural requirement for the uptake of phenethylamine derivatives by rat platelets. Although none of these phenethylamine derivatives induce platelet shape change, they inhibit serotonin-induced shape change and serotonin uptake with the same relative potency (tyramine greater than phenethylamine greater than or equal to dopamine). This suggests that the receptors controlling serotonin uptake and serotonin-induced shape change have a common structural component that binds phenethylamine derivatives. However, the fact that phenethylamine derivatives activate the serotonin uptake mechanism but do not induce platelet shape change suggests that serotonin uptake and serotonin-induced shape change are mediated by two distinct activation sites of serotonin receptors.

Animals↗
PubMed1980

Inhibition of dopamine-beta-hydroxylase by alternative electron donors.

The alternative electron donors ferrocyanide and hydroquinone have been shown to also act as inhibitors of dopamine-beta-hydroxylase (3,4-dihydroxyphenylethylamine, ascorbate:oxygen oxidoreductase (beta-hydroxylating), EC 1.14.17.1). Hydroquine shows uncompetitive inhibition with respect to ascorbate and competitive inhibition with respect to tyramine. Ferrocyanide shows uncompetitive inhibition with respect to ascorbate and mixed type inhibition with respect to tyramine. Inhibition by ferrocyanide at concentrations at or above 2.5 . 10(-5) M was prevented by 2.5 . 10(-6) M cupric ion. These results indicate that the inhibitory action of these alternative electron donors is due to their interaction with a reduced enzyme species. The potency of inhibition of dopamine-beta-hydroxylase by both ferrocyanide and hydroquinone is dependent on the degree of protonation of a group in the enzyme having a pKa of 5.3.

Ascorbic Acid↗
PubMed1983

Potentiation of the biochemical effects of beta-phenylethylhydrazine by deuterium substitution.

The concentrations of dopamine (DA), m-tyramine (mTA), p-tyramine (pTA) and serotonin (5-HT) in the striata of rats 18 hr after the administration of three different doses (5, 50, or 100 mg/kg) of beta-phenylethylhydrazine (phenelzine, PEH) were measured. These concentrations were compared to those following the administration of the same doses of 1,1,2,2-tetradeutero-PEH (d4PEH). In general, PEH and d4PEH caused dose-dependent increases in the levels of mTA, pTA and 5-HT. The lowest dose of d4PEH caused greater increases than PEH in the levels of all four monoamines. The concentration of 5-HT was increased more by d4PEH than PEH at all three doses. The inhibition of mitochondrial MAO obtained from rat striatum by PEH or d4PEH in vitro revealed no differences. However, the inhibition of striatal MAO obtained from rats injected with d4PEH was found to be greater than that from rats injected with PEH. It was concluded that deuteration of PEH potentiates its ability to inhibit MAO following its administration to the rat by slowing its degradation in vivo.

Animals↗
PubMed1986

Studies on the uptake and release of propranolol and the effects of propranolol on catecholamines in cultures of bovine adrenal chromaffin cells.

Uptake and release of [3H]l-propranolol and the effects of propranolol on the uptake and release of [3H]norepinephrine were studied in cultures of isolated bovine adrenal chromaffin cells. [3H]l-Propranolol uptake increased with increasing [3H]l-propranolol concentration from 10(-7) M to 10(-3) M and was not saturable in this concentration range. [3H]l-Propranolol uptake was equally inhibited by l- and d-propranolol, indicating that the uptake is not stereoselective. [3H]l-Propranolol uptake differed from [3H]norepinephrine uptake in two respects: [3H]l-propranolol uptake was 44-50 times greater than [3H]norepinephrine uptake at early non-equilibrium time periods, and [3H]l-propranolol uptake was not Na+ dependent and was not inhibited by desipramine, indicating that [3H]l-propranolol is not taken up by the biogenic amine transport system. In cells preloaded with [3H]l-propranolol, two agents, veratridine and tyramine, stimulated an increased release of [3H]l-propranolol into the medium. However, veratridine-induced [3H]l-propranolol release was inhibited only slightly by the Na+ channel blocker tetrodotoxin, and tyramine-induced [3H]l-propranolol release was not inhibited by desipramine. In addition, K+, carbachol and the physiological mediator of adrenal catecholamine release, acetylcholine, failed to evoke [3H]l-propranolol release. Therefore, it is unlikely that propranolol is released in response to physiological stimulation of adrenal chromaffin cells in animals administered propranolol in vivo. l-Propranolol inhibited [3H]norepinephrine uptake by chromaffin cells with an IC50 for l-propranolol of 5 X 10(-6) M; d-propranolol was equally potent for this effect at lower propranolol concentrations. By themselves, neither l- nor d-propranolol had any effect on [3H]norepinephrine release from the cells. However, l-propranolol inhibited carbachol-induced [3H]norepinephrine release with an IC50 for l-propranolol of 5 X 10(-7) M to 10(-6) M. At these lower concentrations, d-propranolol had no effect on carbachol-induced [3H]norepinephrine release, indicating that the inhibition by l-propranolol may be mediated via beta-adrenoceptors on chromaffin cells.

Acetylcholine↗