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  • 1
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  In this study the role of retinal dopamine (DA) receptors in the light-induced suppression of melatonin biosynthesis in the chicken pineal gland was examined. Exposure of dark-adapted chickens to low intensity light (4 lux) at night significantly decreased the activity of serotonin N-acetyltransferase (AA-NAT; the penultimate and key regulatory enzyme in melatonin production) and melatonin content in the pineal gland. This suppressive action of light was blocked by intraocular (i.oc.) administration of SCH 23390 (a selective antagonist of D1-DA receptors), but was not affected by sulpiride (a selective antagonist of D2-DA receptors). Injection of DA (i.oc.) to dark-adapted chickens significantly decreased pineal AA-NAT activity and melatonin content in a dose- and time-dependent manner. The action of DA was mimicked by selective agonists of D1-DA receptors, SKF 38393 and SKF 81297, and non-hydrolyzable analogs of cyclic AMP (cAMP), dibutyryl-cAMP and 8-bromo-cAMP. However, i.oc. administration of quinpirole, a selective agonist of D2-DA receptors, did not modify pineal AA-NAT activity. In contrast, quinpirole potently decreased nocturnal AA-NAT activity in the retina. Systemic administration of SCH 23390 to chickens blocked the i.oc. DA-evoked decline in nighttime pineal AA-NAT activity, whereas sulpiride was ineffective. These findings indicate that light activation of retinal dopaminergic neurotransmission, with concomitant stimulation of D1-DA receptors positively coupled to the cAMP generating system, plays an important role in a cascade of events regulating pineal activity.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The duck pineal gland rhythmically produces two 5-methoxyindole compounds, i.e. 5-methoxytryptophol and melatonin. 5-Methoxytryptophol levels are low at night and high during the day, while melatonin concentrations are high at night and low during the day. The melatonin rhythm reflects oscillations in the activity of serotonin N-acetyltransferase (AA-NAT; a penultimate and key regulatory enzyme in the melatonin biosynthetic pathway). The activity of hydroxyindole-O-methyltransferase (HIOMT; an enzyme involved in the synthesis of both 5-methoxytryptophol and melatonin) does not exhibit any significant rhythmic changes throughout the 24-hr period. Plasma levels of melatonin exhibited daily changes that were parallel to fluctuations in pineal melatonin content. Although plasma concentrations of 5-methoxytryptophol were low in ducks, they showed daily variations. The mean 5-methoxytryptophol concentration between zeitgeber time 9 (ZT9) and ZT15 was 2.4-times higher than the mean value for samples collected between ZT18 and ZT3. These findings indicate that in the duck the pineal production of 5-methoxytryptophol and melatonin may be inversely correlated.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The objective of the present studies was to define the enzyme systems catalysing the 6-hydroxylation of melatonin, by monitoring the levels of 6-sulphatoxymelatonin in rat hepatic postmitochondrial preparations and in precision-cut liver slices. Melatonin 6-hydroxylase activity was localized in microsomes and was supported by NADPH, but not NADH. Treatment of rats with β-naphthoflavone more than tripled 6-sulphatoxymelatonin formation from melatonin, but gave rise only to a moderate increase (25%) in the sulphate conjugation of 6-hydroxymelatonin. Treatment of rats with phenobarbitone, acetone, dexamethasone and clofibrate did not increase 6-sulphatoxymelatonin generation when either melatonin or 6-hydroxymelatonin served as substrates. Of a number of cytochrome P450 inhibitors investigated, only furafylline inhibited markedly the conversion of melatonin to 6-sulphatoxymelatonin without any concomitant effect on the sulphoconjugation of 6-hydroxymelatonin. When liver slices were incubated with melatonin, treatment of rats with β-naphthoflavone, and to a lesser extent phenobarbitone, elevated the levels of 6-sulphatoxymelatonin in the culture medium. No such increase was seen when slices from β-naphthoflavone-treated rats were incubated with 6-hydroxymelatonin, whereas a modest increase was seen with slices from phenobarbitone-treated rats. Treatment of rats with acetone, dexamethasone or clofibrate failed to modulate the levels of 6-sulphatoxymelatonin generated from either melatonin or 6-hydroxymelatonin. Molecular modelling analysis revealed that melatonin had a high area/depth2 ratio, displayed characteristics of CYP1A2 substrates and could be readily accommodated into the human CYP1A2 active site in a position favouring 6-hydroxylation. Collectively, all the above data provide strong experimental evidence that CYP1A2 is an important catalyst of the 6-hydroxylation of melatonin.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 23 (1997), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Nicholls J, Skene DJ, Hourani SMO. Use of a newly developed technique to isolate rat pinealoeytes and study the effects of adenosine agonists on melatonin production. J. Pineal Res. 1997; 23:164–168. © Munksgaard, Copenhagen〈section xml:id="abs1-1"〉〈title type="main"〉AbstractRecent studies have suggested a role for adenosine in the regulation of rat pineal melatonin synthesis. The data, however, are conflicting and therefore the aim of this study was to characterize adenosine receptors more fully in vitro by using a range of selective adenosine agonists and the adenosine antagonist 8-sulphophenyltheophylline (8-SPT). A simple method for the mechanical separation of rat pinealoeytes was developed. Pinealoeytes were briefly (15 min) incubated with drugs followed by a 4 hr drug-free incubation period after which melatonin concentrations in the incubation medium were measured by radioimmunoassay. The β-adrenoceptor agonist isoprenaline gave a dose-related increase in melatonin production, demonstrating that this pinealocyte preparation technique is suitable to evaluate the effect of drugs on pineal melatonin synthesis. Our results show that adenosine, N6-(phenylisopropyl)adenosine (R-PIA) and 2-p-(2-carboxethyl) phenethylamino-5 '-N-ethylcarboxamidoadenosine (CGS21680) did not affect melatonin synthesis alone or in combination with isoprenaline. However 5'-N-ethylcarboxamidoadenosine (NEC A) (100 uM) potentiated the stimulatory effect of isoprenaline (3 μM) on pineal melatonin production and this effect appeared to be antagonized by 8-SPT (50 uM). These results are consistent with activation by NECA of an A2b adenosine receptor.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the chick pineal gland, 5-methoxytryptophol and melatonin concentrations fluctuate in a rhythmic manner. These rhythms are circadian in nature persisting in constant darkness and have opposite phases. Acute exposure of chicks to white light (30 lux for 5, 10, 20, and 30 min) at night increased the amount of pineal 5-methoxytryptophol and decreased pineal melatonin content. A 6 hr pulse of light (100 lux) applied early in the subjective night (CT12–CT18) caused a delay in the phase of the circadian rhythms of 5-methoxytryptophol and melatonin by 3.7 and 4.5 h, respectively, compared to untreated controls. When the 6 hr light pulse was given during the late subjective night (C18–CT24) it advanced the phase of the 5-methoxytryptophol and melatonin rhythms by 8.1 and 11.9 h, respectively. In the chick pineal the phase-advancing effects of light on the circadian rhythms of 5-methoxytryptophol and melatonin were more pronounced than the phase-delaying effects. Our results provide the first evidence that light is capable of phase shifting the 5-methoxytryptophol rhythm in a manner similar to its action on the melatonin rhythm.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Munksgaard International Publishers
    Journal of pineal research 38 (2005), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract:  Noradrenaline (NA) levels in pineal gland of chickens at various posthatching stages (P2, P4, P8, P15, P30 and P57) were determined by high-performance liquid chromatography with electrochemical detection. Pineal NA content markedly increased between P2 and P30. P30 and P57 chickens, kept from the day of hatching under a 12:12 hr light-dark (LD) illumination cycle, exhibited rhythmic changes in pineal NA, with levels in the dark period being markedly higher than in the light period. In younger birds pineal NA concentrations did not show pronounced daily variations. In 4-wk-old chickens (P28–30) kept under constant darkness (DD), the rhythmic pattern of pineal NA persisted for 1 day (with higher values during the subjective dark phase than during the subjective light phase), but this disappeared 24 hr after the introduction of DD. In contrast, NA content in pineal glands isolated from birds maintained for 2 days under continuous light was similar to that found during the light phase of the LD cycle, and did not exhibit significant rhythmicity. In P30 chickens, pretreated with α-methyl-p-tyrosine (AMPT, an inhibitor of tyrosine hydroxylase, the key regulatory enzyme in the biosynthesis of catecholamines), pineal NA content declined slowly and monophasically during the light phase. During the dark phase the AMPT-induced decay of NA was biphasic – namely an initial rapid decline over the first 15 min which was followed by a slow-rate decline – an observation indicating that NA turnover was higher in the dark. Acute exposure of the dark-adapted P30 and P57 chickens to light significantly decreased pineal NA content, but did not affect pineal NA concentrations in younger birds. Our results suggest that the NA rhythm in the chicken pineal gland and its sensitivity to light regulation progressively develop during the first month of life.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 8 (1990), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The daily pattern of the major urinary metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s), was determined in women prior to having a breast biopsy. Women with malignant tumors appeared to have significantly lower 24 h concentrations of aMT6s with a decrease in the amplitude of the rhythm compared to women with benign tumors. The amount of urinary aMT6s was dependent upon the age of the subject but was not affected by either menopausal status or body mass index. However, when the women with malignant tumors were compared with a large group of normal women of the same age their aMT6s levels were not outside the normal range. The results show that a large control group and very accurate age matching are essential when investigating melatonin production in different groups of subjects.
    Type of Medium: Electronic Resource
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