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L Peyrin

Publications and source records attributed to L Peyrin.

At least 55 records · Page 3Linked to original sources

Urinary MHPG sulfate as a marker of central norepinephrine metabolism: a commentary.

Measurement of total (free + conjugated) 3 methoxy-4-hydroxyphenylglycol (MHPG) in urine has long been used to assess the metabolism of central norepinephrine (NE). However, available data indicate that total MHPG is not a sensitive marker because the portion of urinary MHPG which derives from brain NE is less than was previously assumed. Several arguments support the view that central MHPG excretion is best represented by the urinary MHPG sulfate fraction. Accordingly, a new strategy has been introduced in last years, involving the separate determination of sulfate and glucuronide conjugates of MHPG as respective markers of central and peripheral NE metabolism. Various biochemical and pharmacological data obtained in healthy subjects and in patients with mental diseases support this hypothesis.

Adult↗

Conjugation and deamination of circulating dopamine: relationship between sulfated and free dopamine in man.

In order to assess the importance of conjugation in dopamine metabolism, we infused dopamine (20 nmol/kg/min, 1 h) to seven male subjects, then measured the kinetics of free and conjugated dopamine and DOPAC (deaminated dopamine) in plasma both during and after the infusion. Dopamine increased as early as 2 min after the start of the infusion, then reached a plateau and remained elevated on a level of 25 times the basal value. Dopamine sulfate and DOPAC followed very similar patterns and increased continuously from the 30th and 20th min, respectively, until the end of the infusion (5.18- and 5.76-fold, respectively), but only dopamine sulfate remained elevated (1.65-fold) on the first day following infusion. DOPAC glucuronide increased moderately (2.58-fold) at the end of the experiment, but neither dopamine glucuronide nor DOPAC sulfate were increased despite high precursor circulating levels. Free DOPAC and dopamine sulfate levels during infusion were correlated with dopamine levels when all subjects were pooled. In addition, within a subject dopamine sulfate to dopamine correlations were found with slopes varying in a range of 1 to 15. Our results show that sulfation is significantly involved in the metabolism of circulating dopamine and is not easily saturated, suggesting that dopamine sulfate may be an index of endogenous dopamine release.

3,4-Dihydroxyphenylacetic Acid↗

Catecholamines and fuels after an ultralong run: persistent changes after 24-h recovery.

This study examined the alterations induced by an ultralong distance run (169 +/- 6 km in 24 h) and by prolonged postrace recovery (24 h) on blood fuel metabolites and catecholamines in seven trained subjects. Ten minutes after the race, plasma concentrations of glycerol and free fatty acids (FFA) were decreased twofold. Plasma glucose was unchanged. Plasma concentrations of free norepinephrine (NE) and free dopamine (DA) increased from 2.73 +/- 0.28 to 5.41 +/- 1.11 nmol.l-1 and from 0.45 +/- 0.13 to 0.62 +/- 0.18 nmol.l-1 whereas free epinephrine (E) and insulin were unchanged; 24 h after the race, plasma glycerol and FFA concentrations remained elevated (twofold) and TG decreased twofold compared with resting levels. Concomitantly, plasma NE and DA levels remained elevated, respectively, 6.23 +/- 0.41 and 0.77 +/- 0.13 nmol.l-1. These data show that the alterations in circulating fuel metabolites and NE induced by the ultralong race were still present 24 h later. The involvement of lipid metabolism and catecholamines in processes of post-exercise recovery is discussed.

Adult↗

Urinary free and conjugated catecholamines and metabolites in autistic children.

Urinary catecholamines (DA, NE, E) and their main metabolites (HVA, DOPAC, MHPG) were analyzed both as free and conjugates in eight children diagnosed as autistic according to DSM-III criteria and eight normal children. Significant differences appeared for the urinary excretion of both DA and NE and their respective metabolites: Autistic children showed low DA, high HVA, high NE, low MHPG urinary levels. These results are consistent with previous findings on altered catecholamine metabolism in autistic children. They suggest that autistic behaviors might be related to an abnormal functional imbalance among monoamines either at a molecular level or at a system level. Furthermore, they emphasize the special interest of urinary assays in pediatric research.

3,4-Dihydroxyphenylacetic Acid↗

Long-term hypoxia increases the turnover of dopamine but not norepinephrine in rat sympathetic ganglia.

The content and turnover of dopamine, 3,4-dihydroxyphenylacetic acid and norepinephrine have been investigated in the superior cervical, coeliac and mesenteric ganglia of rats exposed to moderate normobaric hypoxia (10% O2 in N2) lasting for 2-28 days. the turnover was estimated by the decrease in amine contents after inhibition of catecholamine biosynthesis with alpha-methyl-p-tyrosine. In all 3 sympathetic ganglia, long-term hypoxia elicited a sustained increase in the content and turnover of dopamine. In contrast, the content and turnover of norepinephrine remained unchanged, except for a moderate increase in the coeliac ganglion after 14 and 28 days of hypoxia. These results suggest that the dopamine and norepinephrine pools in ganglia have a different functional significance and that rat sympathetic ganglia contain a pool of dopamine specifically sensitive to long-term hypoxia.

3,4-Dihydroxyphenylacetic Acid↗

Relationships between catecholamine or 3-methoxy 4-hydroxy phenylglycol changes and the mental performance under submaximal exercise in man.

Eleven young students were tested to determine the relationship between the improvement of mental performances observed under prolonged submaximal work and central or peripheral catecholamine changes. The subjects pedaled a bicycle ergometer for 1 h at a work load individually calculated to approximate 75% of maximal oxygen uptake. The mental test, consisting of 1-h sessions of time-limited word tests and arithmetical calculations, required a high degree of concentration (vigilance and short-term memory). Catecholamines [epinephrine (E), norepinephrine (NE), dopamine (DA)], metanephrine (MN), normetanephrine (NMN) and the glucuronide conjugate of 3-methoxy 4-hydroxyphenylglycol (MHPG) were assayed in urine to assess peripheral activity: E and MN as indexes of adrenomedullary secretion, NE, NMN and MHPG glucuronide as markers of NE metabolism in sympathetic nerves. Urinary MHPG sulfate was determined as a possible marker of central noradrenergic metabolism. When compared to the effect of single tests, the combination of prolonged submaximal work and mental task induced significant increases in MHPG sulfate and E + MN excretions. Both these increases were correlated each to one another and also correlated to the number of discriminated words. Altogether, the present data show that prolonged submaximal work under mental load activates catecholamine systems and suggest that a relationship exists between adrenomedullary activation and the improvement of mental performance. Based on literature data, the possible modulatory role of peripheral E on mental processes and central noradrenergic activity is discussed.

Adult↗

Differential effect of guanethidine on dopamine and norepinephrine pools in urine, heart and superior cervical ganglion in the rat.

The time-related changes of dopamine (DA) and norepinephrine (NE) pools were investigated in heart, superior cervical ganglion (SCG) and urine in rats treated chronically with guanethidine (50 mg/kg i.p. five days each week). The efficiency of sympathectomy was assessed by the great loss of NE in heart and superior cervical ganglion (SCG) (-96% and -76% respectively of control values on day 18) together with the ready reduction of NE and 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine. The pattern of changes was quite different for DA, which was less readily affected and at a lesser extent than NE in heart and SCG thus suggesting the presence of norepinephrine-independent DA stores. Similarly the urinary excretion of free DA, free 3,4-dihydroxyphenylacetic acid (DOPAC) and free homovanillic acid (HVA) was slightly decreased only from the 9th day, whereas urinary conjugated DA remained unaltered. These results indicate that the greatest portion of urine free and conjugated DA, free DOPAC and free HVA derives from peripheral pools located outside noradrenergic neurons. Alternatively, the time-course of DA sensitivity to guanethidine suggests that a portion of urine DA may originate from DA stored independently from NE in noradrenergic neurons.

Animals↗

Dopamine and norepinephrine dynamics in rat carotid body during long-term hypoxia.

The contents of dopamine (DA), norepinephrine (NE) and 3,4-dihydroxyphenylacetic acid (DOPAC), and the utilization rates (secretion plus breakdown) of DA and NE were measured in carotid bodies of rats exposed, to normobaric hypoxia (10% O2 + 90% N2) for 0, 2, 7, 14 or 28 days. Long-term hypoxia elicited gradual increase in DA, NE and DOPAC contents, which after 28 days were increased 27, 51 and 4.6 fold, respectively. The DA utilization rate estimated after blockade of biosynthesis by alpha-methyl-p-tyrosine gradually increased from two days to the end of hypoxic exposure. The utilization rate of NE was unaltered within the first 7 days but was greatly increased after 14 and 28 days. It was concluded that the utilization rates of both DA and NE were increased by long-term hypoxia but these increases had different time courses. Dopamine, whose utilization increased in the early stage of hypoxia, might exert neurochemical effects on the chemoreceptors throughout the exposure, whereas NE, whose utilization was stimulated after two weeks of hypoxia, might play a significant role only after a delay.

3,4-Dihydroxyphenylacetic Acid↗

Inhibitory effect of almitrine on dopaminergic activity of rat carotid body.

Almitrine increases ventilation by stimulating the peripheral arterial chemoreceptors. This study assessed the effects of acute and chronic almitrine treatments on the dopamine (DA) and norepinephrine (NE) contents and utilization rates in the rat carotid body. Almitrine (5 mg/kg ip) caused a 34% reduction in DA content after 30 min. Extending the almitrine treatment for 15 days (one daily ip injection) produced a further progressive diminution in DA stores (-55%; P less than 0.01). The utilization rate of DA measured after inhibiting catecholamine biosynthesis by alpha-methyl-p-tyrosine was strongly reduced by almitrine (-98% after 15 days; P less than 0.01). The effects of almitrine were dose dependent. The noradrenergic activity was much less altered by the drug. The data showed that almitrine can modify the dynamics of DA in rat carotid body producing a decrease in both content and utilization rate.

Almitrine↗

Sustained enhancement of the catecholamine dynamics in rat carotid bodies, adrenals, sympathetic ganglia and target organs under long-term moderate hypoxia.

The effects of normobaric hypoxia (10% O2) for 2, 7, 14 and 28 days on the dopamine (DA), norepinephrine (NE) and epinephrine (E) dynamics (content and utilization) were investigated in carotid bodies, adrenals, heart, kidneys and three sympathetic ganglia. The results indicate that long-term hypoxia elicited a complex and sustained stimulation of the sympathoadrenal system. Four striking features were evidenced: 1) In carotid bodies, the DA, and with a delay, the NE dynamics were greatly enhanced; 2) in sympathetic ganglia, DA was the only catecholamine whose metabolism was enhanced, suggesting a chemosensitive DA pool in ganglia; 3) in nerve terminals (heart and kidneys), at variance with ganglia, the stimulation under hypoxia was evidenced by the increase in NE metabolic rate; 4) no adaptation of the sympathoadrenal activity occurred after 28 days of hypoxia, except, perhaps, for adrenals.

Adrenal Glands↗

Biochemical evidence for norepinephrine stores outside the sympathetic nerves in rat carotid body.

Adult rats were submitted to pharmacological or surgical sympathectomy. The chronic administration of guanethidine caused tremendous reductions in the norepinephrine stores in heart and superior cervical ganglion due to the destruction of the sympathetic nerve fibers and cell bodies. Guanethidine-sympathectomy resulted in a 70% loss of norepinephrine in the carotid body, whereas the dopamine and DOPAC contents were unaltered. The surgical sympathectomy induced by removing the superior cervical ganglion led to similar results. The present data indicate that a considerable part of norepinephrine in the rat carotid body is stored in the sympathetic nerves. In addition, a significant part of norepinephrine resides outside the sympathetic nerves, probably within the glomus cells.

3,4-Dihydroxyphenylacetic Acid↗

Striatal and mesolimbic dopaminergic contribution to 3,4-dihydroxyphenylacetic acid sulfate in rat plasma.

Free and sulfated 3,4-dihydroxyphenylacetic acid (DOPAC) were measured in rat plasma after bilateral 6-hydroxydopamine lesions of striatum or mesolimbic tissue (nucleus accumbens + olfactory tubercle). Both lesions selectively reduced plasma DOPAC sulfate levels without altering free DOPAC or catecholamine levels in plasma, sympathetic ganglia or adrenal medulla. The present work confirms our previous findings and suggests that DOPAC sulfate functional state of striatal and mesolimbic dopaminergic neurons.

3,4-Dihydroxyphenylacetic Acid↗

Free and conjugated 3,4-dihydroxyphenylacetic acid and homovanillic acid in brain dopaminergic areas at basal state and after pipotiazine activation.

We have determined free and conjugated 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in discrete brain areas of rats. Conjugated HVA or DOPAC accounted for 22-38% of total acids in striatum, mesolimbic tissue or prefrontal cortex. Activation of dopamine (DA) metabolism by a single injection of pipotiazine palmitic ester (PPZ), a long-lasting neuroleptic, increased free acid levels (DOPAC and HVA) at either dose and conjugate levels after 32 or 50 mg/kg. 48 hours after PPZ-32 mg/kg, the observed increases of conjugates could exceed in some cases those of corresponding free acids. About half of total DOPAC and HVA were conjugated in hypothalamus, PPZ moderately increased free DOPAC (at 32 mg/kg) but did not elevate significantly the conjugated form. It is concluded that sulfation is an important pathway for DOPAC and HVA metabolism in brain and that the determination of both free and conjugated DOPAC or/and HVA may shed additional lights on regional DA metabolism and the effect of drugs thereon.

3,4-Dihydroxyphenylacetic Acid↗

Peripheral distribution of free dopamine and its metabolites in the rat.

Free dopamine (DA) and its metabolites, homovanillic acid (HVA) and 3-4 dihydroxyphenylacetic acid (DOPAC), have been measured and compared with norepinephrine (NE) concentrations in rat peripheral tissues using high performance liquid chromatography with electrochemical detection (HPLC-ED). Detectable amounts of DA and its metabolites were found in all the analyzed tissues. The highest levels were found in carotid body, sympathetic ganglia, urogenital tract and heart, the lowest in liver and lung. DA and DOPAC distribution was heterogeneous and unrelated to NE concentration. Both the variable value of the DA/DA+NE ratio and the presence of DA metabolites in peripheral tissues indicate that a portion of DA may be stored outside noradrenergic neurons and directly catabolized in specific DA pools.

3,4-Dihydroxyphenylacetic Acid↗

Catecholamines of endoneurial laryngeal paraganglia in the rat.

The catecholamines in the recurrent and superior laryngeal nerves of the rat were assayed by high performance liquid chromatography. The nerves were shown to contain high levels of dopamine (1.9 +/- 0.6 and 2.3 +/- 0.4 pmol, respectively) and noradrenaline (1.3 +/- 0.3 and 0.9 +/- 0.2 pmol, respectively). No adrenaline could be detected in any of the nerves. Reserpine markedly depleted the stores of these amines in both nerves. A significant increase in dopamine level was seen in the superior laryngeal nerve after treatment with a monoaminoxidase inhibitor, but not in the recurrent laryngeal nerve. The high levels of dopamine detected are presumably derived from endoneurial paraganglia which were demonstrated by glyoxylic acid-induced fluorescence. The source of noradrenaline is less evident, but noradrenaline is probably stored in both endoneurial paraganglia and in sympathetic nerve endings.

Animals↗

[Conjugation of catecholamines: basic and physiopathological aspects].

In man, the major portion of plasmatic and urinary catecholamines is found in a conjugated/sulfate form. The biological characteristics of the conjugates (formation sites, kinetics of appearance and disappearance from the plasma, genetic regulation, influence of biological factors) are different from those of the free forms. Physiopathological data show that the dosage conjugated catecholamines together with that of free amines, provides interesting informations on the integrative level of sympathetic activity and on the regulation of the catecholamines plasma concentrations by conjugation. In these two objectives, the dosage of DA sulfate proves very important.

Binding Sites↗