摘要:

Abstract:Melatonin binding sites were characterized in human blood lymphocytes. The specific binding 2‐[125I]iodomelatonin ([125I]MEL) to human lymphocytes was dependent on time and temperature, stability, saturation, and reversibility. Moreover, guanine nucleotides decreased the specific binding of [125I]MEL to crude membranes of human lymphocytes, suggesting the coupling of these binding sites to a guanosine nucleotide binding regulatory protein(s). In competition studies, the specific binding of [125I]MEL to lymphocytes was inhibited by increasing concentrations of native melatonin. Scatchard analysis showed that data were compatible with the existence of two classes of binding sites: a high‐affinity site with a Kd of 5.20 ± 0.79 nM and a binding capacity of 50.6 ± 11.0 fmol/107cells, and a low‐affinity site with a Kd of 208.5 ± 50.2 nM and a binding capacity of 2691 ± 265 fmol/107cells. However, concentration‐dependent binding of [125I]MEL to lymphocytes was saturable and resulted in a linear Scatchard plot, suggesting binding to a single class of binding sites. The Kd for the single site was 1.02 ± 0.34 nM with a binding capacity of 10.1 ± 1.6 fmol/107cells. Their affinities closely correlated with the production of cyclic nucleotides, suggesting a physiological role for the melatonin binding sites. Thus, melatonin potentiated the effect of vasoactive intestinal peptide (VIP) on cyclic AMP production (ED50= 1.9 nM) and stimulated cyclic GMP accumulation (ED50= 125 nM). Results demonstrate the existence of two binding sites for [125I]MEL in human blood lymphocytes, with a high‐affinity binding site coupled to the potentiation of the effect of VIP on cyclic AMP production and a low‐affinity binding site coupled to activation of cycl

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1992.tb00034.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:An 18‐year‐old blind man suffered from chronic sleep disturbances associated with daytime fatigue and excessive daytime somnolence. After two unsuccessful treatment regimens with 5 mg and 10 mg melatonin administered at bedtime (2200–2230), a third regimen of 5 mg melatonin administered at 2000 for 3 weeks resulted in a successful resolution of his sleep disturbances. We suggest that the efficacy of melatonin in ameliorating sleep disturbances because of alterations in circadian rhythmicity may be dependent on the time of administr

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1992.tb00035.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Plasma melatonin was measured in lizards (Podarcis sicula) at six different times of day under conditions of constant temperature and darkness. Intact animals showed a circadian rhythm of melatonin with a peak in the subjective night of 207 pg/ml (median) and a trough during the subjective day that was below the minimum detection level of the assay (50 pg/ml). Pinealectomy abolished the circadian rhythm of plasma melatonin; median levels were near or below the minimum detection level at all times sampled. The data suggest that the pineal is the only source of rhythmic blood‐borne melatonin inPodarcis sicula, and are consistent with the hypothesis that changes in the free‐running period of the locomotor rhythm induced by pinealectomy in this species are due to withdrawal of rhythmic melatonin from the bl

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1992.tb00036.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:It has been demonstrated that antitumor immune response is an IL‐2‐dependent phenomenon. Moreover, experimental results suggest the existence of interactions between IL‐2 and the pineal gland, which also plays a role in the control of immunity and cancer growth.Alterations of both IL‐2 and melatonin secretion have been reported in cancer patients. To further investigate pineal/IL‐2 relationships in humans with cancer, we evaluated the melatonin rhythm in seven advanced small cell lung cancer patients, before and at weekly intervals during immunotherapy with IL‐2, given subcutaneously at a daily dose of 3 × 106IU/m2 twice daily for 5 days/week for 4 weeks. Before IL‐2, no patient showed a light/dark rhythm of melatonin. IL‐2 administration induced a normalization of the melatonin circadian rhythm, with the appearance of a night time peak in 4/7 patients. This effect, however, disappeared with IL‐2 interruption in 3/4 patients. This preliminary study, by showing that IL‐2 may restore a normal melatonin rhythm, suggests that the anomalous pineal function in cancer may depend at least in part on the altered endoge

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1992.tb00037.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:A chemical analysis was instigated to investigate the identity of the luteinizing hormone (LH)‐like immunoactivity present in ovine pineal protein homogenates. Isolation of pineal LH‐like material was accomplished using a 0.1 M ammonium sulphate (pH 4.0) extraction followed by anion‐exchange chromatography. The resulting 3.0 M ammonium sulphate precipitate containing 70% of the LH‐like immunoactivity was refractionated by cation‐exchange and Sephadex G‐100 chromatography. Analysis of the pattern of recovered LH‐like immunoactivity in the Sephadex G‐100 eluate indicated the presence of molecular weight (MW)<60,000 besides MW 21,000 species of LH‐like proteins. Bioactivity was tested in the rat Leydig cell steroidogenesis assay. In terms of steroid production, the activity was associated with the MW 21,000 LH‐like proteins only. Further purification by CM‐Sephadex chromatography and gel permeation HPLC was conducted in order to determine whether the physicochemi‐cal properties of pineal LH‐like material represented endogenous LH, synthesized and released by the ovine pituitary. It is concluded by a variety of means, including polyacrylamide gel electrophoresis, and amino acid and carbohydrate analyses, that at least two molecular forms of immunoactive LH‐like proteins occur in ovine pineal tissue. The M W 21,000 forms showed much similarity with ovine adenohypophyseal LH or with a complex mixture of its subunits. These observations contribute to the understanding of endocrine‐endocrine transducing events

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1992.tb00038.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:Diurnal variations in serum melatonin levels and pineal concentrations of serotonin (5‐HT),N‐acetylserotonin (NAS), 5‐hydroxyindole acetic acid (5‐HIAA), and melatonin were estimated in adult male Djungarian hamsters kept under long‐day (LD 16:8) or short‐day (LD 8:16) photoperiods. The nocturnal increase in melatonin production was accompanied by a marked drop in pineal serotonin concentrations. Serotonin levels, however, decreased approximately 4 hr before pineal melatonin increased. Correlations of the mean values for pineal serotonin and pineal melatonin indicated significant correlations at both LD 16:8 (r = ‐0.92, P<0.001) and LD 8:16 (r = ‐0.85, P<0.001). The mean levels of pineal serotonin and serum melatonin were correlated as well (LD 16:8, r = ‐0.91, P<0.001; LD 8:16, r = ‐0.81, P<0.01). The levels of pineal serotonin declined at approximately the same time as serum melatonin levels increased. These data suggest that the drop in pineal serotonin is primarily a consequence of melatonin production (as reflected by increasing serum concentrations). Consequently, pineal concentrations of melatonin may not be the best estimate of actual melatonin production, but a measure of how much melatonin is accumulated within the pineal due to high synthesis rates while the release of the hormone from t

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1992.tb00039.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract:The biological effects of administering melatonin into the mediobasal hypothalamus (MBH) was documented in adult Soay rams using two delivery systems: (1) microimplants in the MBH delivering melatonin continuously and (2) microdialysis probes in the MBH delivering melatonin intermittently as a daily timed infusion. The experimental protocol was to precondition rams to long days (LD 16:8) for 10 to 12 weeks, and then introduce the exogenous source of melatonin by implantation or infusion. Sixteen rams were divided equally into four treatment groups: (a) microimplants in the MBH, (b) microdialysis probes in the MBH, (c) empty microimplants in the MBH to act as sham‐operated controls, and (d) no surgery to act as unoperated controls. The microimplants consisted of 22‐gauge stainless steel cannulae with melatonin fused inside the tip and were placed bilaterally in the brain for 14 weeks. These implants had previously been shown to release melatonin at a relatively constant rate when incubated in buffered saline at 37°C (3.42 ± 0.42 μg/24 hr, mean ± SEM, 1–10 weeks) and to produce a localised concentration of melatonin when implanted in the brain (localised to within 1 mm of the center of the implant). The microdialysis probes were also 22‐gauge cannulae with a 3 mm membrane (Biotech). They were placed bilaterally into the MBH, connected to two portable syringe drivers secured to a backpack. Melatonin was infused daily for 10 hr (estimated delivery: 0.5 μg/hr) starting in the mid‐light phase to produce a long‐duration intermittent melatonin signal. Technical problems limited the period of infusions to 8–10 weeks with minor interruptions. Animals from all groups were maintained on long days, and the observations extended for a period of 28 weeks. The melatonin implants placed in the MBH induced a premature increase in the blood concentrations of FSH and growth of the testes. This treatment also induced a marked decrease in the plasma concentrations of prolactin and the earlier development of the long winter pelage. These changes were reversed after the end of treatment with a decline in the plasma concentrations of FSH and regression of the testes, and an increase in the concentrations of prolactin and moult of the winter pelage. Daily infusions of melatonin from the microdialysis probes in the MBH produced qualitatively similar, but less marked responses. The overall results illustrate that the administration of melatonin into the MBH, either continuously or intermittently, to extend the duration of the daily melatonin signal, induces multiple short‐day responses. The dialysis technique provides a potential way to investigate the mechanism of action of melatonin since it is possible to simultaneously administer melatonin and sample dial

ISSN:0742-3098    

DOI:10.1111/j.1600-079X.1992.tb00040.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY