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PubMedDate not supplied

Tyramine-induced contractions in the rabbit ear and basilar arteries.

This study examined in vitro tyramine (TY)-induced contractions of the isolated ring segments of the rabbit basilar and ear arteries in relation to their sympathetic innervations. The TY dose--response relationship in the basilar artery was not affected by cocaine, chronic sympathectomy, or reserpine pretreatment. However, these treatments shifted the TY dose--response relationship in the ear arteries significantly to the right. These results indicate that the TY-induced contraction in the basilar artery is due solely to its direct stimulation of the postsynaptic alpha-receptors, but in the ear artery it is due both to its indirect [release of norepinephrine (NE)] and direct actions. The failure of TY to induce contraction in the basilar artery by the indirect mechanism is probably in part due to a wide synaptic cleft distance and the reported insensitivity of alpha-receptors of this artery. These results suggest that the endogenous NE releasable from the sympathetic nerve in the basilar artery is insufficient to bring about vasoconstriction. This is turn favors our previous hypothesis that transmural-nerve-stimulation (TNS)-induced constriction of this artery is to a transmitter other than NE. It further suggests that the functional significance of the sympathetic innervations to different regions of the vessels is highly variable even when they are of the same ganglionic origin.

Animals↗
PubMedDate not supplied

The effect of age on the tyramine-sensitive intraneuronal pool of norepinephrine in rat heart.

The effect of age on the amount of norepinephrine (NE) released by tyramine (TYR) was investigated in hearts from Fischer 344 rats, 6, 12, and 24 months of age. Isolated hearts were perfused through an aortic cannula with Krebs-Ringer solution containing 1.6 X 10(-4) M TYR. alpha-Methyl-p-tyrosine (7.5 X 10(-5) M) and fusaric acid (10(-5) M) were added to inhibit de novo synthesis of NE. The effluent from the heart was collected continuously throughout 4 h of perfusion with TYR. The content of NE in the perfusion effluent was measured by electrochemical (EC) detection methods after alumina extraction and high-performance liquid chromatography (HPLC) separation. In addition, the amount of NE remaining in the heart after TYR perfusion was measured with HPLC/EC methodology. The amount of NE released from hearts was not significantly different among the ages [6 months, 612.5 +/- 68.2 ng; 12 months, 640.2 +/- 53.0 ng; 24 months, 593.8 +/- 38.2 ng; p greater than 0.05, analysis of variance (ANOVA)]. These amounts represent more than 93% of total cardiac NE at all ages (6 months, 97.6 +/- 0.5%; 12 months, 94.8 +/- 1.3%; 24 months, 93.7 +/- 1.7%). The t1/2 for the decline in NE in hearts was also similar at the three ages (6 months, 45.0 +/- 4.9 min; 12 months, 53.6 +/- 5.2 min; 24 months, 60.4 +/- 7.8 min; p greater than 0.05, ANOVA). These results indicate that the amount of NE released by TYR does not change with increasing age.

Aging↗
PubMed1983

A comparison of diclofensine and desmethylimipramine using tyramine pressor tests in normal subjects.

Eight male volunteers received placebo, diclofensine 25 mg, diclofensine 50 mg and desmethylimipramine (DMI) 50 mg at least a week apart. Using tyramine pressor tests, no statistically significant differences between the noradrenaline reuptake blocking effects of the three active treatments could be demonstrated. Visual analogue rating scales showed an increase in dryness of the mouth at 3 h after DMI but no similar effect after either dose of diclofensine.

Adult↗
PubMed1988

Uptake and intracellular transport in rat liver of formaldehyde-treated bovine serum albumin labelled with 125I-tyramine-cellobiose.

1. Endocytosis of formaldehyde-treated bovine serum albumin by rat liver sinusoidal cells has been followed by injecting rats with the protein labelled with 125I-tyramine cellobiose (125I-TCfBSA). 125I-TCfBSA is quickly taken up by the liver; the radioactivity present in the organ reaches a plateau 5-10 min after injection and is maintained for up to at least 180 min. During the first 5 min most of radioactivity remains acid-precipitable. After which, labelled acid-soluble components are produced at a constant rate for up to 30-40 min. 2. Differential centrifugation shows that radioactivity is first recovered mainly in the microsomal fraction. Within a few minutes it exhibits a distribution pattern similar to that of lysosomal enzymes, being chiefly located in the mitochondrial fractions. 3. Isopycnic centrifugation in a sucrose gradient of the microsomal fraction isolated 1 min after injection indicates a similar distribution for radioactivity and alkaline phosphodiesterase. Later, the microsomal radioactivity distribution curve is shifted towards higher densities and becomes distinct from that of the plasma-membrane enzyme. After isopycnic centrifugation in a sucrose gradient of the total mitochondrial fraction a considerable overlapping of acid-precipitable and acid-soluble radioactivity distributions is observed without significant changes with time. The same is observed in a Percoll gradient except that after a relatively long time (greater than 30 min) of injection a marked shift of radioactivity distribution towards higher densities occurs. 4. A pretreatment of rats with Triton WR 1339, a density perturbant of liver lysosomes, causes a striking shift of acid-soluble radioactivity distribution in a sucrose gradient towards lower densities while having markedly less influence on the acid-precipitable distribution. As a result, a distinction between the distribution of both kinds of radioactivity becomes clearly apparent. A preinjection of yeast invertase, modifies the acid-soluble distribution without having a significant effect on the acid-precipitable distribution up to 30 min after 125I-TCfBSA injection. 5. Glycyl-1-phenylalanine-2-naphthylamide largely releases acid-soluble radioactivity associated with the mitochondrial fraction, whatever the time after 125I-TCfBSA injection. On the other hand the proportion of acid-precipitable radioactivity present in the fraction that can be released is almost zero at 10 min after injection, and it later increases. 6. The results presented here are best explained by supposing that, after being trapped in small pinocytic vesicles, 125I-TCfBSA is quickly delivered to the endosomes.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Differential interaction of 1-methyl-4-phenylpyridinium ion with the putatively vesicular binding site of [3H]tyramine in dopaminergic and nondopaminergic brain regions.

The neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) in the brain striatum has recently been shown to bind at a putatively vesicular site labeled by [3H]tyramine ([3H]TY). Whereas in the rat and mouse striatum MPP+ antagonized TY binding competitively, in the cerebellum there was a mixed-type antagonism, which suggests the simultaneous occupancy of two different sites. Ki values from displacement curves revealed a fourfold difference in the affinity of MPP+ for TY sites in the two brain regions. The degeneration of central noradrenergic terminals induced by an intraperitoneal injection of the toxin N-(2-chloroethyl)-N-ethyl-2- bromobenzylamine in rats decreased by 80% the maximal number of cerebellar TY binding sites, while not affecting striatal binding. Furthermore, guanethidine, a marker for noradrenaline (NA) vesicles, potently inhibited TY binding in NA-innervated regions, such as the cerebellum and the parietal cortex, and poorly in the striatum. It is concluded (a) that both MPP+ and TY may also label NA vesicles and (b) that the vesicular carriers for dopamine and NA have different characteristics, which may underlie a regional specificity in the rate of endovesicular sequestration of MPP+, with either neurodegenerative or neuroprotective consequences, depending on the brain area involved.

1-Methyl-4-phenylpyridinium↗
PubMed1978

Release of [3H-noradrenaline from the motor adrenergic nerves of the anococcygeus muscle by lysergic acid diethylamide, tyramine or nerve stimulation.

1 A method is described for labelling the neuronal noradrenaline (NA) stores of rat anococcygeus with [3H]-NA and detecting subsequent release of 3H from the superfused tissue by nerve stimulation or drugs. 2 Lysergic acid diethylamide (LSD) or tyramine but not barium chloride or carbachol increased the efflux of 3H although each drug produced an equivalent contractile response. This confirms that LDS has an indirect sympathomimetic action. 3 LSD was found to produce a proportionately smaller reduction of the nerve-induced efflux of 3H than of the accompanying contractile response. 4 The inhibition of nerve-induced contractile responses by LSD was shown to be independent of the neuronal uptake of noradrenaline and any post-junctional inhibition demonstrated to be non-specific.

Animals↗
PubMed1986

High affinity binding of [3H]-tyramine in the central nervous system.

Optimum assay conditions for the association of [3H]-para-tyramine [( 3H]-pTA) with rat brain membranes were characterized, and a saturable, reversible, drug-specific, and high affinity binding mechanism for this trace amine was revealed. The binding capacity (Bmax) for [3H]-pTA in the corpus striatum was approximately 30 times higher than that in the cerebellum, with similar dissociation constants (KD). The binding process of [3H]-pTA involved the dopamine system, inasmuch as (a) highest binding capacity was associated with dopamine-rich regions; (b) dopamine and pTA equally displaced specifically bound [3H]-pTA; (c) there was a severe loss in striatal binding capacity for [3H]-pTA and, reportedly, for [3H]-dopamine, following unilateral nigrostriatal lesion; (d) acute in vivo reserpine treatment markedly decreased the density of [3H]-pTA and, reportedly, of [3H]-dopamine binding sites. In competition experiments [3H]-pTA binding sites, though displaying nanomolar affinity for dopamine, revealed micromolar affinities for the dopamine agonists apomorphine and pergolide, and for several dopamine antagonists, while having very high affinity for reserpine, a marker for the catecholamine transporter in synaptic vesicles. The binding process of [3H]-pTA was both energy-dependent (ouabain-sensitive), and ATP-Mg2+-insensitive; furthermore, the potencies of various drugs in competing for [3H]-pTA binding to rat striatal membranes correlated well (r = 0.96) with their reported potencies in inhibiting [3H]-dopamine uptake into striatal synaptosomes. It is concluded that [3H]-pTA binds at a site located on/within synaptic vesicles where it is involved in the transport mechanism of dopamine.

Animals↗
PubMed1989

The influence of amine metabolizing enzymes on the pharmacology of tyramine in the isolated perfused mesenteric arterial bed of the rat.

1. The pressor response to the infusion of tyramine (Tyr) into the isolated perfused mesenteric arterial bed of the rat has been studied at both a low and a high dose (0.2 and 2.0 mumol) and the effect of monoamine oxidase-A (MAO-A) and semicarbazide-sensitive amine oxidase (SSAO) inhibition was examined. Very little MAO-B activity is found in homogenates of this tissue when Tyr is used as substrate. 2. Inhibition of SSAO by treating rats with 1 mg kg-1 (E)-2-(3',4'-dimethoxyphenyl)-3-fluoroally lamine (MDL 72145) 1 h before dissection, had no significant effect on the maximum pressure attained or the area under the curve (AUC) of the response to both low and high doses of Tyr. Inhibition of MAO-A, by inclusion of 10 microM clorgyline in the perfusing fluid, resulted in no significant potentiation at both low or high doses of Tyr. The inhibition of both these enzymes together substantially increased the AUC of the pressor response. 3. Cocaine (3 microM) significantly potentiated the responses to adrenaline (Ad). At this dose, cocaine significantly reduced the peak height and the AUC of the responses to both doses of Tyr. 4. Inhibition of extraneuronal uptake mechanisms with corticosterone (29 microM) did not potentiate the response to Ad and did not significantly alter the response to Tyr (low dose). 5. The effects of MDL 72145 and clorgyline on the directly acting amine, Ad, were studied. MDL 72145 caused a small but significant increase in the EC50 and in the maximum response to Ad, whilst clorgyline (10 microM) increased the EC50 value slightly and decreased the maximum response.

Animals↗
PubMed1978

The indirect sympathomimetic activity of etilefrine--a comparison with tyramine and ephedrine using [3H] noradrenaline.

The indirect sympathomimetic activity of etilefrine has been examined using the ventral caudal artery of the rat. This vessel has a rich sympathetic innervation and lends itself to studies on [3H]noradrenaline efflux from these sites. Etilefrine possessed significant indirect activity on the artery and this action, although less than that of tyramine, was equivalent to that caused by ephedrine. Pretreatment of the vessels with a mixture of iproniazid, doca, cocaine and UO521 (3',4'-dihydroxy-2-methyl propiophenone) significantly enhanced[3H]-noradrenaline efflux from the artery.

Animals↗
PubMed1994

Studies on the mechanism of spasmolytic activity of (O-methyl-)-N-(2,6-dihydroxybenzoyl)tyramine, a constituent of Aniba riparia (Nees) Mez. (Lauraceae), in rat uterus, rabbit aorta and guinea-pig alveolar leucocytes.

The mechanism of action of a nonspecific smooth muscle relaxant, (O-methyl-)-N-(2,6-dihydroxybenzoyl)tyramine (riparin), a constituent of Aniba riparia (Nees) Mez. (Lauraceae) was studied in relation to Ca2+ metabolism in smooth muscle tissues and in guinea-pig alveolar leucocytes. In rat depolarized uterus, riparin inhibited in a reversible and noncompetitive manner CaCl2-induced contraction, a response mediated through voltage-dependent Ca2+ channels. The pD2 value (mean +/- s.e.m.) for riparin was 4.98 +/- 0.06. When compared with sodium nitroprusside (IC50 2.5 microM), an antagonist of receptor-operated Ca2+ channels, riparin was ineffective in suppressing noradrenaline-induced sustained contractions of rabbit aortic strips. However, in the aorta, the compound inhibited intracellular calcium-dependent transient contractions of noradrenaline and riparin (IC50 10.1 microM) was approximately two and a half times more potent than procaine (IC50 25.5 microM) a known inhibitor. In guinea-pig alveolar leucocytes, riparin (IC50 3.2 microM) inhibited intracellular Ca2+ accumulation induced by the calcium ionophore A23187. The results suggest that the inhibition of Ca2+ influx and of Ca2+ release from intracellular stores contribute to the spasmolytic effects of riparin, which may not involve cyclic AMP generation as the levels of this nucleotide were not increased in alveolar macrophages treated with riparin (10-100 microM).

Animals↗
PubMed1968

Tyramine-H3: deaminated metabolites in neuroblastoma tumors and in continuous cell line of a neuroblastoma.

Neuroblastoma tumors, as well as cultured cells of neuroblastoma, contain high monoamine oxidase activity. The major deaminated metabolite of tyramine-H(3) in the incubation mixtures with the tumors or with the cultured cells is p-hydroxyphenylacetaldehyde. Upon addition of reduced nicotinamide-adenine dinucleotide phosphate, the aldehyde was further metabolized by the reductive pathway to p-hydroxyphenylethanol, whereas upon addition of nicotinamide-adenine dinucleotide phosphate the aldehyde was only metabolized to a minor extent by the oxidative pathway to p-hydroxyphenylacetic acid. Aldehyde dehydrogenase activity is very low in the neuroblastoma tumors and in the cultured neuroblastoma cells. The generation of aldehydes and alcohols by the action of monoamine oxidase suggests that the deaminated metabolites of biogenic amines might exhibit some toxic effects in neuroblastoma patients.

Alcohols↗
PubMed1960

Tyramine-producing streptococci in neonatal diarrhoea.

An outbreak of neonatal diarrhoea associated with large numbers of Streptococcus faecalis var. zymogenes is described.A follow-up survey showed that 23.3% of 347 healthy babies carried this organism without ill effect. The tyrosine decarboxylase activity of the streptococci from both sick and healthy babies was identically high. It is suggested that the tyramine-producing activity of these streptococci was not the primary cause of the diarrhoea.

Child↗
PubMed1990

High incidence of endogenous depression in migraine: confirmation by tyramine test.

Forty patients with migraine who were attending a specialist clinic were interviewed with the Schedule for Affective Disorders and Schizophrenia--Lifetime version. Sixteen (40%) had a history of major depression which was of endogenous type in 15, according to Research Diagnostic Criteria. The tyramine test, a previously established trait marker for endogenous depression, showed that the migraine group as a whole had significantly low values compared with 14 normal controls, due almost entirely to low values in the endogenous depressive subgroup; there were no differences between diet-sensitive and non-diet-sensitive migraine patients. Thus depression in patients with migraine seems unlikely to be secondary to migraine per se. A substantial subgroup of patients with migraine may possess an inherent predisposition to endogenous depression.

Adult↗
PubMed2005

Tyramine and octopamine: ruling behavior and metabolism.

Octopamine (OA) and tyramine (TA) are the invertebrate counterparts of the vertebrate adrenergic transmitters. They are decarboxylation products of the amino acid tyrosine, with TA as the biological precursor of OA. Nevertheless, both compounds are independent neurotransmitters that act through G protein-coupled receptors. OA modulates a plethora of behaviors and peripheral and sense organs, enabling the insect to respond correctly to external stimuli. Because these two phenolamines are the only biogenic amines whose physiological significance is presumably restricted to invertebrates, pharmacologists have focused their attention on the corresponding receptors, which are still believed to represent promising targets for new insecticides. Recent progress made on all levels of OA and TA research has enabled researchers to understand better the molecular events underlying the control of complex behaviors.

Animals↗
PubMed1992

Accumulation of 125I-tyramine cellobiose-labeled low density lipoprotein is greater in the atherosclerosis-susceptible region of White Carneau pigeon aorta and further enhanced once atherosclerotic lesions develop.

Previous studies have suggested that greater arterial concentrations of undegraded low density lipoprotein (LDL) and/or greater arterial rates of LDL degradation may play role(s) in determining regional differences in arterial susceptibility to atherosclerosis in rabbits (Schwenke and Carew, Arteriosclerosis 1989;9:895-918). The White Carneau (WC) pigeon is also useful for investigating potential mechanism(s) that might account for regional variation in arterial susceptibility to atherosclerosis because atherosclerosis develops predictably in the aorta at the level of the celiac bifurcation (atherosclerosis-susceptible celiac site). In this study we sought to determine whether the 125I-tyramine cellobiose (125I-TC) content 1 day after injecting 125I-TC-LDL ("125I-TC-LDL accumulation") would be greater in the celiac site in arteries of WC pigeons and whether 125I-TC-LDL accumulation would be exaggerated by cholesterol feeding. Because 125I-TC remains trapped in cells after cellular degradation, arterial sites that either degrade LDL at higher rates or contain higher concentrations of undegraded LDL or both will demonstrate greater 125I-TC-LDL accumulation. Young WC pigeons were studied while consuming a cholesterol-free diet and after consuming a cholesterol-containing diet for 1, 2, 4, and 8 weeks. In pigeons fed a cholesterol-free diet, 125I-TC-LDL accumulation in the celiac site was equivalent to 0.24 +/- 0.02 micrograms LDL cholesterol/cm2 aortic surface/day compared with only 0.14 +/- 0.02 micrograms LDL cholesterol/cm2/day for the adjacent aorta, which is resistant to atherosclerosis (atherosclerosis-resistant site) (p less than 0.025). In atherosclerotic lesions excised from the celiac site, 125I-TC-LDL accumulation was equivalent to 21 +/- 10 micrograms LDL cholesterol/cm2 aortic surface/day compared with 0.66 +/- 0.17 micrograms LDL cholesterol/cm2/day for the adjacent atherosclerosis-resistant site (p less than 0.001). During cholesterol feeding, 125I-TC-LDL cholesterol accumulation in the celiac site as a whole increased 30-fold compared with a fivefold increase in plasma LDL cholesterol. In comparison, 125I-TC-LDL cholesterol accumulation in the adjacent atherosclerosis-resistant arterial site increased at the same rate as the plasma LDL cholesterol, while 125I-TC-LDL cholesterol accumulation in two other relatively atherosclerosis-resistant arterial sites that we studied increased relatively little during cholesterol feeding. The results of this study suggest that differences in arterial 125I-TC-LDL accumulation, both those present in normal animals and those induced by cholesterol feeding, may contribute to the characteristic regional variation in arterial susceptibility to atherosclerosis in WC pigeons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Autoradiographic analysis of the distribution of 125I-tyramine-cellobiose-LDL in atherosclerotic lesions of the WHHL rabbit.

It is well established that plasma lipoproteins enter the artery wall and play a role in the atherogenic process. However, it is still unclear where within developing atherosclerotic lesions lipoproteins accumulate and which arterial cells participate in the metabolism of these lipoproteins. For this reason, light and electron microscopic autoradiograms were prepared from sections of lesioned aortas of Watanabe heritable hyperlipidemic (WHHL) rabbits 44 hours after injection of 125I-tyramine cellobiose-low density lipoprotein (TC-LDL). After uptake of 125I-TC-LDL and intracellular degradation of the LDL protein, the nondegradable TC ligand remains trapped and thus demarcates the cells participating in the degradation of LDL. Results of other studies indicate that 48 hours after injection into WHHL rabbits, about one half of the 125I label present in lesions represents accumulated degradation products while the remaining 125I label is present as intact 125I-TC-LDL. The distribution of autoradiographic silver grains was analyzed at low resolution in fatty streaks, transitional lesions, and advanced atheroma. In all cases, the majority of silver grains were associated with superficially located subendothelial macrophage-derived foam cells. In more advanced lesions, labeling was predominant in foam cells situated within the lateral margins of the lesions. Morphometric quantification of the distribution of silver grains in electron photomicrographs of fatty streaks from two young WHHL rabbits strongly supported the data obtained at the light microscopic level. In early fatty streaks from the aortic arch and the thoracic and abdominal aortas, subendothelial macrophage-derived foam cells contained a high proportion of the silver grains (40-60% of the total) and accounted for between 30% and 40% of the lesion volume. In contrast, smooth muscle cells in the lesions contained only 7-10% of the total silver grains and accounted for approximately 20% of the lesion volume. Endothelial cells contained the most silver grains on a per-unit-volume basis by occupying only 1-2% of the lesion volume. However, the endothelium contained less than 5% of the total grains in lesions. The remaining silver grains (25-45%) were associated with the extracellular matrix, which constituted between 40% and 50% of the lesion volume. These data indicate that in the WHHL rabbit, subendothelial macrophage-derived foam cells avidly accumulate and metabolize LDL despite having few functional LDL receptors.

Animals↗
PubMed1973

Maturation of responsiveness to cardioactive drugs. Differential effects of acetylcholine, norepinephrine, theophylline, tyramine, glucagon, and dibutyryl cyclic AMP on atrial rate in hearts of fetal mice.

Freshly isolated hearts of fetal mice of gestational ages ranging between 12 and 22 days (term) were exposed to several concentrations of a variety of chronotropic agents. Acetylcholine (10(-4)-10(-2) M) caused marked bradycardia in all hearts, even after only 12-14 days' gestation (i.e., even before cardiac innervation had occurred), and the intensity of the response increased steadily with advancing age throughout gestation. Responsiveness to norepinephrine was present but minimal at 12-14 days, so that mean atrial rate rose by < 10% with a maximal concentration of the drug (10(-5) M); responsiveness became more marked by 15-16 days (just after the time atrial innervation is thought to begin) and still greater effects appeared just before term. Glucagon had no effect in hearts of < 17 days' gestational age, but caused tachycardia thereafter, indicating that cardiac responsiveness to glucagon differentiates later than does responsiveness to norepinephrine. Responses to theophyl-line in 12-14 day hearts exceeded those to norepinephrine, indicating that the drug can affect heart rate independently of its ability to cause release of endogenous catecholamines. In contrast, tyramine caused no response until 21-22 days, well after the time the beta-receptor has differentiated and after innervation is fairly well developed, suggesting that the drug's primary sympathomimetic effect is indirect rather than direct. Dibutyryl cyclic AMP did not cause tachycardia at any fetal age. It is concluded that maturation of responsiveness of the mouse heart to cardioactive drugs develops in specific patterns for different agents. The identification of differential patterns of maturation for various drugs may provide valuable means for characterizing the differentiation of specific receptors and for investigating possible mechanisms of action of the drugs.

Acetylcholine↗