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Ginseng saponins reduce acetylcholine-evoked Na+ influx and catecholamine secretion in bovine adrenal chromaffin cells.

The effects of various ginseng saponins (ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rh1, Ro and Rs1), which are isolated from the root of Panax ginseng, on the catecholamine secretion from bovine adrenal chromaffin cells stimulated by ACh were examined. Most of the ginsenosides (1-100 microM) had a tendency to reduce the ACh-evoked secretion of catecholamines. The order of inhibitory potency (at the concentration of 10 microM) was as follows: Rg2 > Rf > Re > Rh1 > Rb2, Rg1 > Rb1 > Rc > Rb3, Rd, Ro, Rs1. The inhibition of ginseoside Rg2 at 10 microM was 72%, but ginsenosides Rb3, Rd, Ro and Rs1 did not show the inhibitory effect. On the other hand, ginsenoside Rg2 (1-100 microM) did not at all affect the secretion induced by high K+ or veratridine, a potent specific activator of voltage-sensitive Na+ channels. Ginsenoside Rg2 (1-100 microM) also inhibited both ACh-induced Na+ and Ca++ influxes into the cells in a concentration-dependent manner. The concentration-response curves for ginsenoside Rg2 inhibition of Na+ influx, of Ca++ influx and of catecholamine secretion were quite similar. The inhibitory effect of ginsenoside Rg2 on the secretion was not overcome by increasing ACh or external Ca++ concentrations. These results strongly suggest that the ginseng saponins, especially ginsenoside Rg2, block the nicotinic ACh receptors or the receptor-operated Na+ channels (but not voltage-sensitive Na+ and Ca++ channels), inhibit Na+ influx through the channels and consequently reduce both Ca++ influx and catecholamine secretion in bovine adrenal chromaffin cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Monoamines and the mechanism of antidepressant action: effects of catecholamine depletion on mood of patients treated with antidepressants.

Brain catecholamines can be rapidly reduced by inhibiting their synthesis with alpha-methyl-para-tyrosine (AMPT). In order to assess the role of catecholamines in antidepressant action AMPT challenges were administered in a double-blind, placebo-controlled, crossover fashion to 14 depressed patients having maintained a therapeutic antidepressant response for > or = 2 weeks (3 desipramine, 2 mazindol, 5 fluoxetine, 4 sertraline). Each patient participated in two challenges one week apart. Each challenge included a baseline, two days of either AMPT or diphenhydramine (active placebo), and a followup. Antidepressant drugs were continued throughout testing. The 3 desipramine- and 2 mazindol-responders had a rapid increase in depression score during AMPT but not placebo (diphenhydramine) challenge whereas only 1 of 9 selective serotonin reuptake inhibitor (SSRI)-treated patients did. The implication of this is that the antidepressant response to desipramine may be more acutely dependent on brain catecholamine content than the response to SSRIs. In the context of our previous work with tryptophan depletion, these results suggest that the neurobiological mechanisms underlying the antidepressant responses to different drugs involve alterations in the functioning of different neurotransmitter systems and reinforce the importance of changes in both the serotonin and catecholamine systems for successful antidepressant responses.

Adult↗

[Catecholamine provision and the morphofunctional characteristics of the lymph nodes with different special purposes in acute benzpyrene poisoning].

Using fluorescent histochemical methods of catecholamines detection microfluorometry, morphometry, and classical cytological technique the catecholamine level, the density of adrenergic nerve fibers and cytological composition of the lymph nodes of different localization were studied in rats in health and after intraperitoneal injection of benz(a)pyrene. It has been revealed that exposure to benzpyren leads to decrease of catecholamine level and of the density of adrenergic innervation of abdominal lymph nodes and is accompanied with structural changes (decrease of corticomedullary index as a result of augmentation of the area of medullary sinuses and medullary cords) and cytological content of these organs (increase of plasmocyte counts in medullary cords). The degree of structural reconstructions depends on the primary status of organs and its typological characteristics. Catecholamine-depending reconstruction of the lymph nodes is connected with the place and method of toxic agent injection.

Acute Disease↗

Peripheral catecholamine metabolites and menstrual irregularity in patients with polycystic ovaries.

OBJECTIVE: To investigate the catecholamine status of patients with polycystic ovary syndrome. DESIGN: Three parallel groups with polycystic ovary were diagnosed by ultrasound: (a) 5 patients with regularly ovulatory menstruation; (b) 10 with anovulatory menstruation; (c) 13 with secondary amenorrhea who responded to progestagen with withdrawal bleeding. Blood samples for measurement of LH, testosterone, and catecholamine metabolites were drawn during cycle days 4-7. RESULTS: (1) Serum LH and testosterone of the patient groups (b) and (c) were significantly higher than those of controls. (2) Plasma 3,4-dihydroxyphenylglycol (DOPEG) and the DOPEG/DOPAC ratio were elevated in patients, and DOPAC levels were reduced. However, there was no significant difference of catecholamine metabolites among the three patient groups. CONCLUSIONS: The androgen status in polycystic ovary diagnosed by ultrasound is correlated, but catecholamine status is not correlated, with the menstrual irregularity of polycystic ovary syndrome.

3,4-Dihydroxyphenylacetic Acid↗

Sex differences in catecholamine response to clonidine.

Sex-related differences both in the basal secretion of catecholamines and in the adrenergic reactivity to various stimuli have been described. We studied the responses of catecholamines and arterial blood pressure to clonidine (0.3 mg per os) in 31 normotensive subjects (10 men (M), aged 18-42 years, and 21 women (W), aged 20-48 years). Plasma catecholamines were determined by HPLC at -30, -15, 0, 120, 130, 140 min after clonidine. The basal levels of plasma norepinephrine were similar in men and in women (M = 1.16 +/- 0.26 vs. W = 0.87 +/- 0.07 nmol/l). Basal plasma epinephrine levels were not different in the two sexes (M = 0.21 +/- 0.03 vs. W = 0.14 +/- 0.03 nmol/l). The mean arterial pressure decrease after clonidine was similar in the two groups (M = 13 +/- 3 vs. W = 15 +/- 2 mmHg). The decrease in plasma epinephrine after clonidine was similar in men and women (M = 0.06 +/- 0.04 vs. W = 0.09 +/- 0.02 nmol/l). In contrast, the plasma levels of norepinephrine after clonidine were reduced more in women than in men either when expressed as absolute values (W = 0.63 +/- 0.07 vs. M = 0.3 +/- 0.1 nmol/l; F = 7.6, P < 0.02) or as percentage change (W = 71 +/- 3 vs. M = 34 +/- 8; P < 0.002). The present study demonstrates that an elevated alpha 2-adrenergic activity in women may be responsible for the sexual dimorphism in catecholamine secretion.

Adolescent↗

Biochemical and morphologic study of catecholamine metabolism in spontaneously hypertensive rats.

Catecholamines and catecholamine-synthesizing enzymes have been studied quantitatively in specific brain areas of spontaneously (genetically) hypertensive rats by means of a combination of sensitive enzymatic-isotopic methods and a microdissecting technique. Changes in catecholamine metabolism were found to be localized to regions of the brain implicated in the regulation of blood pressure. Noradrenaline levels were decreased in specific nuclei of the anterior hypothalamus and in the nucleus interstitialis striae terminalis ventralis. The activity of the adrenaline-forming enzyme, phenyl-ethanolamine-N-methyl transferase, was increased in the A1 and A2 areas of the brain stem. These results implicate catecholamine-forming neurons in the hypothalamus and brain stem in the development of spontaneous hypertension in rats.

Animals↗

Anti-arrhythmic protection by ischaemic preconditioning in isolated rat hearts is not due to depletion of endogenous catecholamines.

OBJECTIVES: The present study addresses whether the mechanism of anti-arrhythmic protection by ischaemic preconditioning involves depletion of myocardial catecholamines. METHODS: In a randomised series of studies isolated rat hearts, perfused with whole blood, underwent episodes of regional ischaemia and reperfusion induced with a snare around the left coronary artery. Control hearts (Group 1, n = 12) were subjected to 40 min aerobic perfusion, 30 min ischaemia and 10 min reperfusion. Preconditioned hearts (Group 2, n = 12) were subjected to 10 min aerobic perfusion, three cycles of ischaemia and reperfusion (5 min each), 30 min ischaemia and 10 min reperfusion. Cardiac rhythm was recorded continuously and arrhythmias quantified during the final periods of ischaemia and reperfusion. At the end of the experiment samples of right ventricular (RV; non-ischaemic) and left ventricular (LV; ischaemic territory) tissue were separated and frozen. In 5 additional groups (n = 6/group) tissue samples were taken after 10 min aerobic perfusion, after 10 min aerobic perfusion followed by 1, 2 or 3 preconditioning cycles and after 40 min of aerobic perfusion. All tissue samples were analysed for catecholamine content. RESULTS: Preconditioning resulted in reductions in the incidence of ischaemia-induced VF from 67% in Group 1 to 8% in Group 2, the incidence of ischaemia-induced VT from 100% to 17% and the number of ischaemia-induced VPBs from 246 +/- 25 to 59 +/- 19 (each P < 0.05). The mean content of noradrenaline and adrenaline was consistently higher in RV than LV tissue. Within the LV, however, neither preconditioning nor prolonged ischaemia had any significant effect upon tissue catecholamine content at any time in the experimental protocol. CONCLUSIONS: Depletion of myocardial catecholamines is not involved in the mechanism of anti-arrhythmic protection by ischaemic preconditioning in isolated rat hearts.

Animals↗

[L-DOPA test for evaluating in vivo catecholamine biosynthesis in normal persons and persons with different diseases].

Administration of 1-DOPA into healthy persons increased its excretion with urine and elevated the adrenaline secretion. The increase of catecholamines excretion was not observed in aged patients with hypertension; the data obtained suggest that the synthesis of catecholamines with utilization of DOPA was inhibited. In patients with ulcerous disease excretion of 1-DOPA was not increased after its administration, but secretion of catecholamines was decreased during the day time. Under ulcerous disease 1-DOPA appears to be used in process unrelated to synthesis of catecholamines.

Adult↗

Effect of an aerobic exercise program on blood pressure and catecholamines in normotensive and hypertensive subjects.

Interrelations between physical exercise, monoamines and hypertension are postulated by various investigators. The purpose of the present study was to determine and compare catecholamine levels at rest and after a 12-week aerobic exercise program in 11 sedentary normotensive (N) and 8 hypertensive (H) men. Plasma catecholamines were determined by high performance liquid chromatography with electrochemical detection. A significant post-exercise increase in plasma noradrenaline was observed in the N and H groups (P < 0.01) both before and after the aerobic exercise program. The hypertensive group showed a significant reduction of the sum of 7 skinfold thickness scores after the aerobic exercise program (from 178.7 +/- 65.6 to 144.0 +/- 47.4 mm) although no significant difference was observed when the body mass index was compared. A significant reduction in diastolic blood pressure at rest was observed in the H group after the aerobic exercise program (from 99.2 +/- 2.0 to 85.0 +/- 5.5). There were no significant differences in catecholamine concentrations between groups before and after the 12-week aerobic exercise program at rest and post-exercise. These data show a relationship between physical exercise and hypertension that was not related to changes in plasma catecholamine levels.

Adult↗

[Catecholamines metabolism in extrapyramidal disorders in children].

The author examined the catecholamine metabolism in 78 children with polyetiological extrapyramidal lesions of the nervous system. Most of the cases were with the pallidnigral syndrome. A sharp drop in the catecholamine excretion, especially of the dopamine and DOPA were detected in the akinetico-rigid forms. In torsion muscular deformant dystonia there was the most expressed drop in the DOPA excretion. Under the impact of a pathogenetical treatment by L-DOPA in most of the cases there was an improvement of the clinical state and in the indices of the catecholamine metabolism. A study of the catecholamine metabolism permitted to detect certain aspects in the pathogenesis of different forms of extrapyramidal lesions in children.

Adolescent↗

Ambulatory blood pressure, nocturnal blood pressure reduction and plasma catecholamines.

OBJECTIVE AND DESIGN: Controversial data have been reported on plasma catecholamines in hypertensives. Aims of this study were to find whether 24-hour ambulatory blood pressure was correlated with circulating catecholamines and to investigate whether nocturnal blood pressure reduction was associated with baseline plasma catecholamines. Samples for catecholamine determination were obtained in 34 consecutive male subjects after a 30-minute rest and before ambulatory blood pressure monitoring. RESULTS: Hypertensive patients (n = 22; 24-hour blood pressure: 145 +/- 14/94 +/- 6 mm Hg) showed similar norepinephrine and epinephrine levels when compared with normotensives (n = 12; 24-hour blood pressure: 124 +/- 6/81 +/- 6 mm Hg), and higher dopamine values (hypertensives: 64.6 +/- 58; normotensives: 26.2 +/- 31 pg/ml; p < 0.05). A positive correlation was observed between dopamine and diastolic nocturnal blood pressure (p < 0.05) while a negative correlation was found between dopamine and nocturnal diastolic blood pressure reduction (p < 0.025). No significant relationship was observed between both norepinephrine and epinephrine, and 24-hour blood pressures. CONCLUSIONS: Since previous reports have documented malfunctioning of dopaminergic system in hypertension, the higher levels of circulating plasma dopamine found in hypertensive patients in the present study may account for a peripheral compensatory increase. The correlation between dopamine and nocturnal blood pressure fall seems to indicate that the impairment of dopaminergic system may influence the 24-hour blood pressure profile, affecting the nocturnal blood pressure reduction.

Adult↗

Contrasting mechanisms of adrenal catecholamine release by acetylcholine and high potassium.

Continuous twenty minute exposure of isolated perfused bovine adrenal glands to high potassium concentrations produced shorter durations of catecholamine release than twenty minute continuous stimulation with acetylcholine. Catecholamine release during continuous exposure to potassium decreased linearly on a semilog plot, whereas acetylcholine caused a biphasic release of catecholamine. Glands previously treated with high potassium responded poorly to acetylcholine; however, glands previously treated with acetylcholine showed a maximum response to high potassium concentrations. Full recovery of the response to acetylcholine after high potassium treatment occurred in twenty minutes. High potassium concentrations appear to evoke secretion of "readily releasable" material only, whereas acetylcholine has access to a larger catecholamine store in the adrenal.

Acetylcholine↗

Determination of free and total catecholamines in human urine by HPLC with fluorescence detection.

A simple and highly sensitive method for the determination of free and total (free + conjugated) catecholamines (norepinephrine, epinephrine and dopamine) in human urine is described which employs HPLC with fluorescence detection. Conjugated catecholamines (sulfate form) are hydrolyzed by a sulfatase-mediated reaction to the corresponding free amines. After cation exchange chromatography on a Toyopak IC-SP S cartridge, catecholamines and isoproterenol (internal standard) in urine samples were converted into the corresponding fluorescent compounds by reaction with 1,2-diphenylethylenediamine. These compounds were separated within 8 min on a reversed phase column with isocratic elution using a mixture of water, methanol and acetonitrile containing a Tris-hydrochloric acid buffer (pH 7.0). The detection limit for each catecholamine is ca 2 fmol per 100 microL injection volume.

Adult↗

Innervation of embryonic rat cerebral cortex by catecholamine-containing fibers.

Catecholamine-containing neuronal processes penetrate to the outer superficial layers of the developing neocortex via the lateral neocortex anlage by embryonic day (ED) 16, only 48 hours after the final cell division of the catecholamine neurons in the mesencephalon and pons-medulla. Sagittal sections were taken from a series of perfused embryos at precise time-intervals after insemination. The corpus striatum receives a large catecholamine input and serves as a reference for tracing the very fine varicose processes that course through the caudate nucleus to innervate the more rostral structures of the developing neocortex cerebri. The input fibers to the neocortex arrive via three to four small fiber bundles, entering chiefly at the ventro-rostral aspect. The bundles than bifurcate into the deep and superficial layers of the cortex. Between ED16 to ED21 the innervation progresses in ventral to dorsal and rostral to caudal directions. Embryonically, fluorescent fibers are observed in the outermost superficial layer and in the intermediate zone, below the cortical plate; only rarely are they seen crossing the cortical plate. The demonstration of monoaminergic neuronal fibers reaching neocortical structures by ED16 adds further weight to the speculation that they may play a role in induction and differentiation, and suggests that post-natal experimental manipulations using ascending-bundle lesions will have been performed at least five days after the arrival of catecholamine fibers at their cortical destinations.

Animals↗

Ontogeny of catecholamine systems in the central nervous system of anuran amphibians: an immunohistochemical study with antibodies against tyrosine hydroxylase and dopamine.

To get more insight into developmental aspects of catecholamine systems in vertebrates, in particular anuran amphibians, these systems were studied immunohistochemically in embryos and larvae of Xenopus laevis and Rana ridibunda. Antisera against tyrosine hydroxylase (TH) and dopamine (DA) revealed that catecholamine systems are already present at early embryonic stages. The first dopamine group to be detected was found ventral to the central canal of the spinal cord of Xenopus, soon followed by DA cell groups in the posterior tubercle, the hypothalamic periventricular organ, the accompanying cell group of the periventricular organ, and the suprachiasmatic nucleus. Although weakly TH-immunoreactive cells were found in the olfactory bulb at about the same embryonic stages, DA immunoreactivity was not detected until premetamorphic stage 49. Dopamine cell groups in the caudal brainstem, midbrain, and pretectum appeared at late premetamorphic and prometamorphic stages, whereas the preoptic group was first observed at the metamorphic climax stage. Rana showed an almost similar timetable of development of catecholamine cell groups, except for the caudal brainstem group which was already present at the end of the embryonic period. When compared with previous studies by means of formaldehyde-induced fluorescence technique, it becomes clear that TH/DA immunohistochemistry enables an earlier detection of catecholamine cell groups and fiber systems in anuran amphibians. The present study also revealed that the DA-immunoreactive cells of the hypothalamic periventricular organ never stained with the TH antiserum during development, thus supporting their putatively DA accumulating nature. Another notable result is the site of origin and rather late appearance of the midbrain dopaminergic cell group. It is suggested that the latter cell group only partly corresponds to the ventral tegmental area and substantia nigra of amniotes.

Animals↗

The effects of sleep on circulating catecholamines and aqueous flow in human subjects.

We measured the rate of aqueous flow and analysed its relation to the time of day, the state of wakefulness and the urinary excretion of catecholamines. Two groups of subjects were studied. One group comprised 20 normal subjects who were studied over two 22-hr periods. During one period, the subjects were permitted to sleep during their customary hours of sleep; during the other, they were not permitted to sleep, but remained active for all 22 hr. The other group comprised ten subjects with obstructive sleep apnea who were studied over a 22-hr period and slept during their customary hours of sleep but without the aid of any respiratory device. Aqueous flow was measured with fluorophotometry. Motion of the wrist was monitored by a seismograph (wrist Actigraph) and served as a surrogate of activity and wakefulness. Urinary catecholamine excretion was measured during different periods of the wake/sleep cycle. Both groups exhibited the normal nocturnal suppression of flow (59% lower compared to morning in the normal group; 56% lower compared to morning in the apneic group). During sleep deprivation, the rate of flow at night in normal subjects was 30% lower than during the morning (P < 0.001) and 60% higher than during sleep (P < 0.001). Lid closure during sleep deprivation had no effect on the results. Aqueous flow correlated with a 'catecholamine index', derived from the combined excretion of epinephrine and norepinephrine. Flow also correlated with an 'activity index', and 'sleep efficiency', indices derived from motion of the wrist. We conclude that the day-night difference of aqueous humor flow as measured by clearance of fluorescein from the human eye is driven partly by a factor that has a circadian rhythm and partly by a factor that depends on the activity of the subject. We hypothesize that these factors are the catecholamines, epinephrine and norepinephrine.

Adult↗

Oxidation and nitration of catecholamines by nitrogen oxides derived from nitric oxide.

The reactivity of catecholamines with nitrogen oxides formed from NO in aerated solutions, nitrite, and peroxynitrite was evaluated. Dopamine and norepinephrine in aerobic buffer (pH 7.4) were almost completely converted to their 6-nitro-derivatives by nitric oxide (NO) at room temperature, while epinephrine was nitrated and above all oxidized. The products obtained from each catecholamine treated with sodium nitrite at pH 4-7 were compared to those produced by NO at pH 7.4. Peroxynitrite, which can nitrate tyrosinyl residues, did not produce nitro-derivatives, only oxidized ones. The physiological relevance, particularly for the vascular and nervous system, is discussed. Catecholamine oxidation reactions could be relevant to physiological conditions and also explain neurotoxicity in Parkinson's disease and aging. Nitration reactions, requiring such high NO concentrations, do not seem possible to occur directly under normal physiological conditions, but could take place in acidic vesicules where nitrite, catecholamines, and their nitrated products could accumulate. Finally, the ability of dopamine to increase 2',5'-cyclic adenosine monophosphate (cAMP) formation in cultured striatal neurons was blocked by its nitration by NO or its nitrogen oxide derivatives.

Animals↗

Reduction of plasma catecholamines in humans during clinically controlled severe underfeeding.

BACKGROUND: Sympathetic hyperactivity is one factor for alterations encountered in the plurimetabolic syndrome, a cluster of metabolic abnormalities including obesity, hyperlipidemia, sometimes hyperglycaemia, and hypertonia. It was interesting to know if prolonged severe underfeeding (230 kcal/day) leads to decreases in catecholamines in those patients. METHODS: The plasma concentrations of catecholamines in patients (n = 16) suffering from plurimetabolic syndrome were studied before and during a 16-day period of medically controlled severe underfeeding (230 kcal/day) at rest and in response to exercise. RESULTS: During the period of underfeeding, mean norepinephrine concentrations decreased at rest from 1.45 to 0. 96 nmol/liter, and in response to exercise, from 6.1 to 3.2 nmol/liter. Epinephrine concentrations decreased from 0.15 to 0.1 nmol/liter and from 0.26 to 0.17 nmol/liter, respectively. A significant decrease in catecholamine concentrations was observed only after 16 days of underfeeding. CONCLUSIONS: Clinically controlled underfeeding of patients with plurimetabolic syndrome may result in beneficial clinical and biochemical effects. The findings indicate that relatively long periods of underfeeding induce decreases in plasma catecholamine concentrations. Nevertheless, most of the fall in mean values in norepinephrine and also of the fall in blood pressure values occurred by Day 2. From those tendencies and from the significant changes in both parameters at Day 16 of severe underfeeding one could conclude that altered sympathetic nervous system activity could contribute to the fall in blood pressure.

Adult↗