摘要:

Abstract:The pineal gland of poikilothermic vertebrates originates as an evagination from the diencephalic roof between the habenular and the posterior commissures, and associates with a parapineal organ to form the so‐called pineal complex. The pinealocytes may be photosensitive, secretory or intermediate cells between both. Melatonin, the indoleamine secreted by the pineal, exhibits a circadian secretory rhythm that conveys environmental information to the organism. The peak melatonin secretion occurs during the night, although there are a few examples of an increase in indoleamine secretion during the day. Melatonin is also synthesized in other sites such as the retina, and it has been found in many invertebrates and unicellular organisms. The rhythmic secretory pattern of melatonin is responsible for many biological rhythms exhibited by lower vertebrates. These rhythms are abolished by pinealectomy in some species, but not in others, suggesting the existence of an extra‐pineal pacemaker. The photoperiod and the temperature (especially in reptiles) are the main environmental factors affecting the secretory rhythm of melatonin. Poikilothermic vertebrates exhibit a circadian rhythmic color change, with nocturnal blanching, usually related to melatonin secretion. In amphibians, melatonin exhibits a potent skin lightening activity. However, in fishes and reptiles the melatonin effects vary with the species, the developmental stage, and the pigment cell location. Melatonin also exerts inhibitory or excitatory activity on the amphibian reproductive system, regulation of circadian locomotory activity in reptiles, and modulation of the amphibian metamorphosis. Melatonin has also a modulatory effect on the response of target cells to different hormones and high concentrations or prolonged exposure to the indoleamine may cause autodesensitization in various tissues. Binding sites of melatonin have been detected in the central nervous system and peripheral tissues of various vertebrates. The relative potencies of melatonin analogues demonstrated two subtypes of melatonin receptors (ML‐1 and ML‐2). A transmembrane melatonin receptor has been cloned fromXenopus laevismelanophores; it belongs to the family of the G protein‐coupled receptors and exhibits 85% homology with the mammalian nervous system receptor. Melatonin binding sites in the nucleus of many cell types and its potent intracellular anti‐oxidant action suggest mechanisms of action other than through the G‐protein cou

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00256.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:The antioxidant and possible pro‐oxidant effects of melatonin and related indoleamines (tryptophan, serotonin, N‐acetylserotonin, and 5‐methoxytryptamine) were studied in vitro. In two model membrane systems, i.e., phospholipid liposomes and rat erythrocytes, lipid peroxidation induced by Fe2+and H2O2, respectively, were reduced by the tested indoleamines except for tryptophan. The 5‐hydroxy‐indoleamines, serotonin, and N‐acetylserotonin exhibited pro‐oxidant actions in the bleomycin assay by reducing Fe3+to Fe2+, which leads to DNA damage. The 5‐methoxy‐indoleamines, melatonin and 5‐methoxytryptamine, were devoid of any pro‐oxidant actions in this assay. Serotonin, but not N‐acetylserotonin, scavenged the superoxide anion. None of the indoleamines tested had any reactivity towards H2O2. All the indoleamines, including tryptophan, were, however, shown to react with hypochlorous acid. These findings support an antiperoxidative and antioxidant action of melatonin which is devoid of pro‐oxidant effec

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00257.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Recent studies have shown that melatonin is both hypnotic and hypothermic at physiological levels. Indeed, the hypnotic effect may be mediated via the hypothermic action. If this is the case, it is important to explore the dose‐response relationships for the thermoregulatory effects of melatonin. Four groups of eight healthy adults (n = 32), aged between 18 and 38, each underwent two 12‐hr bedrest protocols in which core body temperature (CT) and plasma melatonin levels were measured concurrently between 0800 and 2000 hr. For each group, subjects ingested either sucrose placebo or a 0.1, 0.5, 1.0, or 5.0 mg melatonin capsule at 1600 hr in a double‐blind counterbalanced cross‐over design. Melatonin was absorbed rapidly, with peak levels being reached after 1 hr at all dose levels. Mean peak plasma melatonin levels increased from physiological to pharmacological levels in a dose‐dependent manner. Elimination for all dose levels was rapid, with mean plasma half‐lives between 33 and 47 min. At the lower doses the mean drop in CT was between 0.05 and 0.15°C and took between 2 and 3 hr. At the higher doses (1.0 and 5.0 mg), CT fell by 0.25–0.3°C within 30–60 min following ingestion and at the highest dose (5 mg) remained suppressed for the duration of the study. While the magnitude and duration of the drop increased in what appeared to be a dose‐dependent manner, it is unlikely that this relationship reflects a simple dose‐response curve. There was considerable variability in plasma profiles following administration, particularly at the two lowest doses (0.1 and 0.5 mg). The lower mean drop in CT probably reflects the lower proportion of subjects achieving physiological plasma levels, and therefore a hypothermic effect, at the two lowest doses. If melatonin is to be used to improve sleep onset and maintenance by lowering CT, doses between 1.0 and 5.0 mg appear to be the lowest that produce a consistent drop in C

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00258.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Successful cloning of melatonin receptors from various target tissues in the past few years has increased our understanding of the molecular signal transduction mechanisms of G‐protein coupled melatonin receptors, of which three subtypes (MEL‐1A, MEL‐1B, and MEL‐1C) have been reported in different vertebrates. Based upon melatonin receptor sequences available in the Genbank database, we have performed phylogenetic analyses of the nucleotide and encoded amino acid sequences of G‐protein‐coupled melatonin receptors, and determined the range of amino acid identities between melatonin receptors of the same and different subtypes. Besides the three well‐known subtypes, a potential novel subtype of MEL‐1D, as exemplified by unique separation ofXenopusX2.0 sequence (Genbank accession No. U31826) from the others in the protein phylogenetic tree, possibly exists. In addition, one of the chicken brain melatonin receptor sequences has been identified as belonging to the MEL‐1B subtype. Our analyses showed that melatonin receptors of the same subtype and different subtypes are likely to share>75% and<65% amino acid identities, respectively. Phylogenetic analysis based on amino acid comparisons will be needed to determine the subtype status of any pair of melatonin receptor sequences that exhibit ≥65% to<75% amino acid identity. Despite the usefulness of genetic relatedness in the subtype classification of G‐protein‐coupled melatonin receptors, functional correlation of molecular structure may ultimately prove the most comprehensive approach in melatonin

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00259.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:In this report, rat hypothalamic nitric oxide synthase (NOS) activity is shown to be partially inhibited by physiological concentrations of the pineal hormone melatonin. In vitro studies demonstrate that 1 nM melatonin, which approximates the physiological concentration of the hormone at night, significantly inhibited NOS activity. In vivo studies show that administering melatonin or collecting the hypothalamus from animals at night, when endogenous melatonin levels are elevated, results in a significant decrease of NOS activity. Results also show that calmodulin may be involved in this process since its presence in the incubation medium prevents the inhibitory effect of melatonin on NOS activity.

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00260.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:Pinealectomy has been shown to alter daily rhythms of neurohypophysial hormone release, with plasma hormone concentrations being elevated in the morning, as compared to intact rats. To determine whether pineal removal also altered the response to known stimuli of hormone release, vasopressin concentrations were measured in control, sham‐operated, and pinealectomized animals during extracellular fluid hypertonicity produced by an intraperitoneal (i.p.) injection of hypertonic saline or hypovolaemia produced by an i.p. injections of polyethylene glycol. In the combined sham‐operated and unoperated groups, injection of hypertonic saline produced a marked increase in plasma vasopressin concentrations from 2.18 ± 0.28 to 7.2 ± 1.24 pmol/liter, but the response was attenuated in pinealectomized animals, concentrations increasing to only 3.4 ± 1.2 pmol/liter. Similarly, following infusion of hypertonic saline, the increase in plasma vasopressin per unit increase in plasma sodium was lower in pinealectomized animals than the pineal intact controls. The response to hypovolaemia was also attenuated, plasma hormone concentrations following reduction in blood volume of approximately 10% increasing to only 3.6 ± 0.6 pmol/liter as compared to 7.3 ± 2.2 pmol/liter in the control groups. There were no significant differences in pituitary vasopressin content in any of the groups studied. Thus, the pineal may influence the vasopressin response to physiological

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00261.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:HydroxyindoleO‐methyltransferase (HIOMT, EC 2.1.1.4) catalyzes the final step in the synthesis of melatonin in the pineal gland and retina. HIOMT mRNA was localized by in situ hybridization in the chicken retina to some, but clearly not all, photoreceptors, while in the pineal gland, most pinealocytes displayed a positive hybridization signal. The in situ hybridization localization was confirmed by immunocytochemistry, using an antibody directed against a synthetic chicken HIOMT peptide. Western blot analysis demonstrated an immunoreactive protein of about 40 kilodaltons in the pineal, but the HIOMT protein was below detectable levels in the retina. However, the HIOMT‐peptide antibody did identify a modestly immunoreactive subpopulation of retinal photoreceptors. These observations suggest that, in the chicken, melatonin biosynthetic activity is located mainly in a subpopulation of retinal photoreceptors and in most pinealocy

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00262.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

Abstract:In this study, the protective effect of melatonin against kainate (KA)‐induced neurotoxicity was evaluated in vitro and in vivo. In rat brain synaptosomes, KA‐induced oxidative stress was measured as shown by significant increases in both the basal generation of reactive oxygen species (ROS), assessed by a fluorescent method, and lipid peroxidation, evaluated as malondialdehyde (MDA) levels. Melatonin decreased, in a concentration‐dependent manner, KA‐induced lipid peroxidation. The intrinsic fluorescence of melatonin molecule hindered the evaluation of its protective effect against KA‐induced ROS generation. However, melatonin was able to reduce FeSO4/ascorbate‐induced ROS generation. The melatonin protective effect was confirmed by in vivo experiments: 73% of rats injected with KA (10 mg/kg i.p.) died within 5 days; melatonin administration i.p. significantly reduced mortality of the animals. The present results suggest that melatonin might be considered a pharmacological agent for the treatment of neurodegenerative

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1996.tb00263.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY