Catecholamines turnover

The turnover rate of a transmitter can be calculated from measurement of either the rate at which it is synthesised or the rate at which it is lost from the endogenous store. Transmitter synthesis can be monitored by administering [ H]- or [ " C]-labelled precursors in vivo these are eventually taken up by neurons and converted into radiolabelled product (the transmitter). The rate of accumulation of the radiolabelled transmitter can be used to estimate its synthesis rate. Obviously, the choice of precursor is determined by the rate-limiting step in the synthetic pathway for instance, when measuring catecholamine turnover, tyrosine must be used instead of /-DOPA which bypasses the rate-limiting enzyme, tyrosine hydroxylase. 

Norepinephrine and epinephrine can be metabolized by several enzymes, as shown in Figure 6-6. Because of the high activity of monoamine oxidase in the mitochondria of the nerve terminal, there is significant turnover of norepinephrine even in the resting terminal. Since the metabolic products are excreted in the urine, an estimate of catecholamine turnover can be obtained from laboratory analysis of total metabolites (sometimes... 

Wise, P.M. (1984). Estradiol-induced daily luteinizing hormone and prolactin surges in young and middle-aged rats Correlations with age-related changes in pituitary responsiveness and catecholamine turnover rates in microdissected brain areas. Endocrinology, 115 801-809. 

Selmanoff MK (1981) The lateral and medial median eminence distribution of dopamine, norepinephrine and luteinizing hormone releasing hormone and the effect of prolactin on catecholamine turnover. Endocrinology 108 1116-1122. 

In studies in man, less direct approaches are necessary and the concentrations of metabolites in CSF have been used to estimate central catecholamine turnover. Several GC-MS assays have been developed for the determination of homovanillic acid (HVA, 4-hydroxy-3-methoxy-phenylacetic acid), the major metabolite of dopamine [457,458,464,465]. 

Sleep. Caffeine affects sleep of older more than it does of younger people and this may be related to the fact that older people show greater catecholamine turnover in the central nervous system than do the young. Onset of sleep (sleep latency) is delayed, bodily movements are increased, total sleep time is reduced, there are increased awakenings. Tolerance to this effect does not occur, as is shown by the provision of decaffeinated coffee. ... 

Kontur PJ, Eechter LD. 1985. Brain manganese, catecholamine turnover, and the development of startle in rats prenatally exposed to manganese. Teratology 32 1 -11. 

Mansky T, Mestres-Ventura P, and Wuttke W (1981) Involvement of GABA of the feedback action of estradiol on gonadrotropin and prolactin release hypothalamic GABA and catecholamine turnover rates. Bram Res 231, 353-364... 

Studies in workers occupationally exposed to manganese have shown positive correlation between homovanillic acid and manganese urinary elimination, which suggests increased catecholamine turnover elicited by Mn (Bucket et al. 1993). In male Rhesus monkeys given 20 mg MgClj per kg body weight x day for 18 months, striatal Mn was elevated from 1.39 0.02 pg/g in the controls to 4.79 0.33 pg/g in the Mn treated animals (Chandra et al. 1979). 

Catecholamine turnover rates were reported to be unchanged except in one study where whole brain noradrenaline turnover was found to be increased (Goiter and Michaelson, 1975). It should be noted that turnover studies utilize the inhibition of an enzyme of transmitter synthesis (usually tyrosine hydroxylase) and measurement of accumulation of catecholaminergic intermediates. If lead were to cause an alteration at the level of the synthesizing enzymes then these methods would be unlikely to detect any lead effect. 

Aleksandrow, D., Januszewicz, Wl. and Wocial, B., Hypotensive effect of aldomet (a-methyldopa) in the treatment of hypertension its effect on the catecholamines turnover, Polskiego Tygodnika Lekarskiego 17, 47 (1962). 

Imipramine blocked the uptake of dopamine at central aminergic neurons in the rat Lithium inhibited the electrically-induced release of NE and 5" in brain slices 3 and did not interfere with the transfer rate of Ma from blood to brain tissue. Data were reported which suggested that the therapeutic effect of electroshock treatment may be due to increased levels of brain amines 5 or to an increase in NE turnover rate . In a study of catecholamine turnover rates in mouse brain it was found that neuroleptics have a predominant influence on dopamine metabolism while antidepressants selectively affect NE metabolism, a higher rate of NE synthesis was found in the forebrain of "mouse-killing" rats over that of controls Imipramine blocked the muricidal behaviour9 and also lowered NE turnover . 

Bacopoulus, NG and Bhatnager, RK (1977) Correlation between tyrosine hydroxylase activity and catecholamine concentration or turnover in brain regions. J. Neurochem. 29 631-643. 

Measurement of catecholamine metabolites can provide insight into the rate of release or turnover of catecholamines in the brain. In clinical studies, metabolites of catecholamines are generally assayed in the CSF because the large quantities derived from the peripheral sympa-thomedullary system obscure the small contribution from the brain to urinary concentrations. However, acid metabolites are actively excreted from the CSF more reliable estimates of turnover in the brain are obtained when this transport process is blocked by pretreatment with the drug probenecid. 

The serotonergic system is not the only monoaminergic neuronal population affected by LSD numerous reports also mention that the turnover of catecholamines is significantly altered in LSD-treated rats. Thus a decrease in cerebral norepinephrine (NE) levels was first reported by Freedman (35) in rats treated acutely with LSD. Tolerance to this action develops rapidly, since LSD no longer... 

Catecholamines Molecular turnover a) Protein kinase mediated phosphorylation of the catalytic peptide —> alteration of kinetic parameter(s) b) Change in Naf ( )... 

Catecholamines Molecular turnover Protein kinase mediated phosphorylation of phospholamban (SR Ca2+-ATPase) or autoinhibitory domain (PM Ca2+-ATPase) relieving negative influence on kinetic parameters... 

Andersson K, Fuxe K, Eneroth P, Isaksson O, Nyberg F, Roos P (1983) Rat growth hormone and hypothalamic catecholamine nerve terminal systems. Evidence for rapid and discrete reductions in dopamine and noradrenaline levels and turnover in the median eminence of the hypophysectomized male rat. Eur J Pharmacol 95 271-275. 

Catecholamines. The quantitative determination of dopamine and noradrenaline in tissue samples of 0.1-10 mg at levels in the order of 0.5 pmol has been described [84]. These methods are based on extraction, formation of the pentafluorpropionyl derivatives, and the use of the homologues, a-methyidopamine and a-methylnoradrenaline as internal standards in SIM. Higher sensitivity than obtainable with fluorimetric or enzymic assays is reported [462J. Applications have been to amine determination in specific regions of rat brain [84] and to measurement of heart ventricle concentrations [463]. A combination of assays of this type with the use of synthesis inhibitors or radioisotope labelled precursors allows direct estimation of brain amine turnover in animals. 

Indolealkylamines. GC-MS methods applied in studies of the biochemical pharmacology of indoleamines parallel work on the catecholamines. SIM assays for serotonin (5-hydroxytryptamine), 5-methoxytryptamine, JV-acetylserotonin and melatonin (5-methoxy-N-acetyltryptamine) in rat pineal and brain tissue have been described [453,469]. Pentafluoro-propionyl derivatives and structural homologue standardisation were employed with detection limits in the subpicomole range. Estimation of central indoleamine turnover in man currently depends upon metabolite determination in CSF. Ion monitoring determination of indole-3-acetic acid [454] a metabolite of tryptamine, and isotope dilution assays for 5-hydroxyindoleacetic acid (5-HIAA) [455,458] have been reported. Serotonin is converted by central monoamine oxidase to 5-HIAA and the measurement of this metabolite, formerly by fluorimetry, is of interest in patients with CNS disorders [470]. GC-MS has also contributed to the identification of N,N-dimethyltryptamine in vitro [471] and isotope dilution technique has been applied to the measurement of this metabolite in control subjects and in psychiatric patients [472]. 

In cirrhotic patients, a reduced synthesis rate of most proteins is found at an early stage, with albumin synthesis being the least compromised factor at first. Fat storage, muscle mass and protein turnover are reduced. This ultimately leads to catabolism (so-called stress metabolism) and increasing muscular atrophy (so-called wasting syndrome). The latter condition can also result from sympathicotonia with elevated catecholamine values similarly, decreased values of IGFl inhibit the formation of muscle tissue. 

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