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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neuroendocrinology 7 (1995), S. 0 
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Melatonin has been proposed to exert some regulatory actions within the pineal gland itself. The present study examined the effect of melatonin on the release of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) from rat pineal glands by using an in vitro perifusion system. Melatonin induced a concentration-dependent stimulatory effect on 5-HT secretion from 10−6 M to 10−3 M. Maximal effects were obtained with melatonin 10−3M and concentrations lower than 10−6 M were without effect. The secretion of 5-HIAA was inhibited by melatonin 10−3 and 10−4M, but it was increased when pineals were incubated with 10−5 and 10−6 M of melatonin. The indoleamine secretion was also studied on peripherally denervated rat pineal glands. Basal output of 5-HT from these glands was increased when compared with those from control rats. In contrast, the secretion of 5-HIAA was strongly reduced after removal of the sympathetic input to the pineal gland. Melatonin 10−3 M failed to stimulate 5-HT release from denervated pineal glands, although it inhibited 5-HIAA secretion. In contrast, melatonin 10−5 M enhanced 5-HT release without altering 5-HIAA output. Fluoxetine, a 5-HT uptake inhibitor, produced similar effects than mM concentrations of melatonin on the indoleamine secretion from control pineal glands, but it had no effect on glands taken from peripherally denervated rats. These data suggest that mM concentrations of the pineal hormone are able to stimulate 5-HT release from the pinealocyte, while mM concentrations of melatonin increase extracellular 5-HT by inhibiting its reuptake in the adrenergic nerve endings. These findings are discussed in relation to the possible role of melatonin regulating the intra- and extracellular availability of 5-HT in the pineal gland and its significance as an autocrine factor.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford : Blackwell Science Ltd.
    Journal of neuroendocrinology 8 (1996), S. 0 
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We recently determined that melatonin stimulated serotonin (5-HT) secretion from rat pineal glands by increasing 5-HT release from the pinealocytes (μM melatonin concentrations) and by inhibiting 5-HT uptake in the pineal sympathetic nerve endings (mM melatonin concentrations). The present study investigated whether a single melatonin injection could alter the content of indoleamines in the rat pineal gland, as well as its possible dependence on the daytime of administration. Melatonin (150 μg/kg) was i.p. injected at 8 time points (11.00 h, 14.00 h, 17.00 h, 20.00 h, 23.00 h, 02.00 h, 05.00 h and 08.00 h) to rats kept in 12:12 h light:dark cycle (lights on at 07.00 h). Melatonin injections in the afternoon (17:00 h) and late in the nighttime (02.00 h and 05.00 h) decreased pineal 5-HT content 90 min later. The levels of 5-hydroxyindoleacetic acid (5-HIAA) were also decreased 90 min after the melatonin treatment at 14.00 h, 17.00 h and 02.00 h. The effect of melatonin on 5-HT content was a long-lasting effect (still evident after 180 min) only when injected at 02.00 h, whereas 5-HIAA levels were found to be decreased 180 min after melatonin treatment at 14.00 h and 23.00 h. No changes in these compounds were detected 240 min after melatonin treatment. Moreover, melatonin did not change 5-hydroxytryptophan levels at any of the daytime points studied. By contrast, 90 min after the injection of melatonin at 20.00 h, an increased content of pineal N-acetylserotonin was observed. This effect of melatonin could be mediated through a phase alteration of the pineal N-acetyltransferase activity rhythm by acting on the suprachiasmatic clock, althought a direct melatonin effect on the pineal rhythmic function cannot be excluded. The effects of the hormone on 5-HT and 5-HIAA contents agree with previous findings on the inhibitory effect of pharmacological doses of melatonin on pineal 5-HT uptake, which presumably would result in a decreased intraneuronal content of 5-HT and its acid metabolite. These data point to an acute regulatory action of exogenous melatonin on the pineal melatonin synthesis pathway which seems to be limited to two daytime phases: the afternoon-early evening period and the second half of the night.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neuroendocrinology 9 (1997), S. 0 
    ISSN: 1365-2826
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This paper describes the effects of β-adrenergic and peptidergic inputs on serotonin (5-HT) synthesis, outflow and metabolism into melatonin in cultured dissociated rat pinealocytes. The spontaneous outflow of 5-HT from pinealocytes was high as demonstrated by the elevated levels of extracellular 5-HT accumulated in the medium (about 5 ng/h/70,000 pineal cells). The β-adrenergic agonist isoproterenol (ISO) used at concentrations up to 10−6 M induced a moderate (+20–40%) increase in intra- and extracellular 5-HT levels together with a large release of melatonin. At a higher ISO stimulation (10−5 M), the intra- and extracellular levels of 5-HT were significantly (−25–30%) reduced whereas melatonin secretion was dramatically increased. This is interpreted as a large 5-HT mobilization for melatonin synthesis and release, consequently reducing both the intracellular pool and outflow of 5-HT. The peptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) up to 10−7 M induced always a moderate (+20–30%) increase in intra- and extracellular levels of 5-HT. However, the use of nM concentrations of VIP or PACAP together with 10−6 M ISO induced a decrease in 5-HT outflow (−25–30%) and a dramatic increase in melatonin secretion as did 10−5 M ISO alone. Neuropeptide Y (NPY) is another pineal peptide which induced a stimulation of 5-HT outflow (+30–40%) although its effect on melatonin release was marginal. The above results are discussed in term of the multineuronal regulation of the synthetic and secretory activities of the rat pineal gland.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Previous studies in Syrian hamster have shown that the correlations between the daily fluctuations in the contents of pineal indoleamines and methoxyindoles are influenced by the photoperiod, and that dopamine may play a role in the regulation of pineal function. The present study investigated the 24 hour changes in the content of 5-hydroxytryptophan (5-HTP), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), N-acetylserotonin (NAS), melatonin, 5-methoxytryptophol (5-MT), noradrenaline (NA), dopamine (DA), and 3,4-dihydroxyphenylacetic acid (DOPAC) in the pineal gland of female Djungarian hamsters exposed to long (LP; LD 16: 8) or short (SP; LD 10: 14) photoperiods for 10 weeks. Pronounced nocturnal increases of N-acetylserotonin and melatonin content were observed irrespective of the photoperiod regime. The content of 5-HT was markedly decreased during the first hour of the night in LP, which contrasted with the lack of changes in NAS and melatonin content at this time. In SP, an increased 5-HTP content and a less obvious decrease in 5-HT content was observed during the night, although melatonin and NAS content were even higher than in LP. Similar daily patterns as for 5-HT were observed in the 5-HT oxidative metabolites (5-HIAA and 5-MT). When considering values throughout the day, a poor correlation for 5-HT vs. NAS and melatonin content was observed, which was particularly evident during the nighttime. These data indicate that the daily variation of pineal indoles may not only be dependent on changes in the N-acetyltransferase activity but also in other mechanisms regulating pinealocyte 5-HT availability. As previously reported in other species of hamster, pineal NA content did not show daily variations in LP conditions, although a nocturnal increase was detected in SP. In contrast, pronounced nocturnal increases were observed in the content of DA and its acid metabolite, DOPAC, irrespective of the photoperiod. These data indicate the existence of an increased dopaminergic turnover during the night and further support a role for DA in the regulation of melatonin synthesis and in the synchronization of the pineal functions.
    Type of Medium: Electronic Resource
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  • 5
    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: Miguez JM, Simonneaux V, Pevet P. The role of the intracellular and extracellular serotonin in the regulation of melatonin production in rat pinealocytes. J. Pineal Res. 1997; 23:63–71. © Munksgaard, Copenhagen〈section xml:id="abs1-1"〉〈title type="main"〉AbstractThis study investigated whether the activation of pinealocyte β-adrenergic receptors is involved in the regulation of serotonin (5-HT) synthesis and release, as it is for melatonin production. In addition, the role of the intra- and extra-cellular 5-HT in modulating the synthesis of melatonin induced by the β-adrenergic agonist isoproterenol (ISO) was also studied. The incubation of dissociated pinealocytes with 0.1–10 IAM ISO resulted in a concentration-dependent increase of melatonin synthesis. 5-HT release and intracellular 5-HT content were increased by 0.1 and 1 μM ISO but they were reduced after ISO 10 μM. Moreover, when incubated with the tryptophan hydroxylase inhibitor p-chlorophenylalanine (PCPA), the secretion of 5-HT as well as the intracellular 5-HT levels were markedly reduced in both ISO-stimulated and unstimulated conditions. Melatonin release was also inhibited by PCPA, although it responded in the expected manner to increasing concentrations of ISO. These data indicate that the release of 5-HT from pinealocytes depends on the availability of cytoplasmic 5-HT, which in turn is highly dependent on the tryptophan hydroxylase activity. In cells stimulated with moderate ISO concentrations, 5-HT release may be an important regulatory process of pineal 5-HT. After a large stimulation of N-acetyltransferase (NAT) activity by ISO, the synthesis of melatonin prevails on 5-HT release, whose decrease is associated to a deficit of intracellular 5-HT. On the other hand, the present study shows that the incubation of pineal cells with high concentrations of 5-HT or with a selective 5-HT2 receptor agonist, α-methyl-5-hydroxytryptamine, reverses partially the inhibitory effect of PCPA on the ISO-stimulated melatonin synthesis. In contrast the 5-HT2 antagonist, ketanserin, results in an inhibiton of the release of melatonin following ISO stimulation. These results suggest that released 5-HT may have a role in the full expression of the β-adrenergically induced NAT activity and, thus, may contribute to the optimal melatonin synthesis at night.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of pineal research 25 (1998), S. 0 
    ISSN: 1600-079X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: : Melatonin content and release from Harderian glands (HGs) has been measured by an in vitro perifusion technique in three rodent species: Wistar rat, Syrian hamster, and Siberian hamster. Melatonin immunoreactive concentrations in HGs of animals killed at 10.00 hr were 0.31 ± 0.031 pg/mg gland in male Wistar rat, 0.54 ± 0.026 pg/mg gland in male Siberian hamster, 0.17 ± 0.070 and 0.20 ± 0.059 pg/mg gland in male and female Syrian hamster, respectively. In all species examined, isolated HGs perifused for 9–15 hr released melatonin but did not stabilize their melatonin release rate. No sex-related difference could be noted in the HG melatonin release rate. The total amount of melatonin released over a 15 hr long perifusion was about 0.075 ± 0.004 ng/15 h/mg gland and 0.063 ± 0.010 ng/15 hr/mg gland in male and female Wistar rat, respectively; 0.155 ± 0.019 ng/15 hr/mg gland and 0.141 ± 0.006 ng/15 hr/mg gland in male and female Siberian hamster, respectively; 0.035 ± 0.003 ng/15 hr/mg gland and 0.045 ± 0.004 ng/15 hr/mg gland in male and female Syrian hamster, respectively. This amount, which is higher than the tissue levels, demonstrates the de novo melatonin synthesis. This is confirmed by the fact that infusion of the indoleamine precursor, tryptophan (TRP), stimulated melatonin secretion from HGs. The melatonin release is increased by 2.5-fold in male and female Wistar rat, 1.5-fold in male and female Siberian hamster, and 2.0- and 3.0-fold in male and female Syrian hamster, respectively. Treatment with a TRP hydroxylase inhibitor, para-chlorophenylalanine, reduced basal melatonin release and inhibited the TRP-induced melatonin stimulation. Kinetics and amounts of melatonin released were not affected by pinealectomy, ruling out a possible plasmatic origin of the HG melatonin. Isoproterenol, a β-adrenergic agonist, and dibutyryl cyclic AMP, a cyclic AMP analogue, failed to stimulate HG melatonin secretion. In conclusion, these results confirm the presence of melatonin in the HGs and demonstrate that melatonin is synthesized in and released from isolated rodent HGs.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0878
    Keywords: Key words: Secretoneurin ; Pineal gland ; Neuropeptide immunocytochemistry ; Sympathetic nervous system ; Superior cervical ganglion ; Pinealocytes ; Cell culture ; Rat (Wistar) ; Syrian hamster ; Mesocricetus auratus ; Siberian hamster ; Phodopus sungorus (Rodentia)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. The pineal gland of mammals is richly innervated by nerve fibres containing various peptides of central or sympathetic origin. In this study, we have investigated the presence, regulation and effect of secretoneurin (SN), a 33-amino-acid peptide discovered recently in the central and sympathetic nervous systems. The rat pineal gland contains about 34 fmol SN/pineal, although only 20% of the secretoneurin immunoreactivity (SN-IR) is the free peptide. SN-IR is localised in only a few nerve fibres found in the parenchyma of the gland and along the pineal stalk. In the rat pineal, SN-IR shows no midday/midnight differences but is significantly decreased (55%–65%) after superior cervical ganglionectomy or exposure to constant light. These observations suggest that, in the rat pineal, SN-IR originates partly from central areas and partly from the superior cervical ganglia. The pineal of the Syrian hamster contains much more SN-IR: 120 fmol SN-IR/pineal (about 20% being the free peptide). SN-IR is found both in nerve fibres and pineal cells. Some of the fibres run along the pineal stalk, indicating that they are of central origin, although a sympathetic origin cannot be ruled out. Pineal SN-IR is below detectable levels in the Siberian hamster. In cultured rat pinealocytes, SN significantly inhibits serotonin release and, to a lower extent, melatonin release.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1573-6903
    Keywords: Melatonin ; serotonin synthesis ; pineal gland ; brain ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This work examined the influence of the pineal gland and its hormone melatonin on the metabolism of serotonin (5-HT) in discrete areas of the forebrain, such as the Striatum and the nucleus accumbens, and the midbrain raphe. The content of 5-HT and its major oxidative metabolite, the 5-hydroxyindoleacetic acid (5-HIAA), as well as the in-vivo tryptophan hydroxylation rate were examined after long-term pinealectomy (one month) and daily melatonin treatment (500 μg/kg; twice daily for ten days) in pinealectomized rats. Pinealectomy did not alter 5-HT content in any of these brain areas, but it significantly increased the content of 5-HIAA in Striatum and the 5-HIAA/5-HT ratio in nucleus accumbens. The normal values of these parameters were recuperated after administration of exogenous melatonin, but it also increased the rate of tryptophan hydroxylation in both areas. In addition, melatonin treatment decreased the levels of 5-HIAA in dorsal raphe nucleus. These data suggest that the pineal gland, through the secretion of melatonin, modulates the local metabolism of 5-HT in forebrain areas by acting on the oxidative deamination. Moreover, melatonin injected in pinealectomized rats derives in a more extended effect than pinealectomy and induces a stimulation of 5-HT synthesis in the striatum, probably due to a pharmacological effect. These results point to the striatum as a target area for the interaction between pineal melatonin and the serotonergic function, and suggest a differential effect of the melatonin injected on areas containing serotonergic terminals and cell bodies, which may relevant for the mode of action of melatonin and its behavioral effects.
    Type of Medium: Electronic Resource
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