Immunomodulatory role of melatonin: specific binding sites in human and rodent lymphoid cells

Calvo, Juan R.; Rafii-EI-ldrissi, Mohammed; Pozo, David; Guerrero, Juan M.

doi:10.1111/j.1600-079x.1995.tb00149.x

Cited by 137 publications

(79 citation statements)

References 55 publications

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“…2 The enzyme activity is regulated by the light/ dark cycle via an adrenergic cAMP control of transcription and proteasomal proteolysis. 3 Other than synchronization of biological functions, melatonin has been suggested to play a role in neurodegenerative diseases such as dementia, 4 in cancer, 5 in the regulation of the immune system, 6 and in some forms of mental illness, especially affective disorders. 7,8 Although most of the proposed protective effects of melatonin are still questionable, the decrease in the melatonin serum concentration in depressed patients has been proven conclusively by several studies.…”

mentioning

confidence: 99%

Differential Effects of Fluvoxamine and Other Antidepressants on the Biotransformation of Melatonin

Härtter¹,

Wang²,

Weigmann³

et al. 2001

Journal of Clinical Psychopharmacology

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Melatonin, the predominant product of the pineal gland, is involved in the maintenance of diurnal rhythms. Nocturnal blood concentrations of melatonin have been shown to be enhanced by fluvoxamine, but not by other serotonin reuptake inhibitors. Because fluvoxamine is an inhibitor of several cytochrome P450 (CYP) enzymes, the authors studied the biotransformation of melatonin and the effects of fluvoxamine on the metabolism of melatonin in vitro using human liver microsomes and recombinant human CYP isoenzymes. Melatonin was found to be almost exclusively metabolized by CYP1A2 to 6-hydroxymelatonin and N-acetylserotonin with a minimal contribution of CYP2C19. Both reactions were potently inhibited by fluvoxamine, with a Ki of 0.02 microM for the formation of 6-hydroxymelatonin and 0.05 microM for the formation of N-acetylserotonin. Other than fluvoxamine, fluoxetine, paroxetine, citalopram, imipramine, and desipramine were also tested at 2 and 20 microM. Among the other antidepressants, only paroxetine was able to affect the metabolism of melatonin at supratherapeutic concentrations of 20 microM, which did not reach by far the magnitude of the inhibitory potency of fluvoxamine. The authors concluded that fluvoxamine is a potent inhibitor of melatonin degradation. Because this inhibitory action is also found in vivo, fluvoxamine might be used as an enhancer of melatonin, which might offer new therapeutic possibilities of fluvoxamine.

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mentioning

confidence: 99%

Differential Effects of Fluvoxamine and Other Antidepressants on the Biotransformation of Melatonin

Härtter¹,

Wang²,

Weigmann³

et al. 2001

Journal of Clinical Psychopharmacology

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“…The time-dependent effects of MLT on the immune system may contribute to time-dependent antitumor effects. Certainly, the specific binding sites of MLT are identified on immune cells (Calvo et al, 1995), and their expression may also show the 24-h rhythm.…”

Section: Discussionmentioning

confidence: 99%

Chronopharmacology of Melatonin in Mice to Maximize the Antitumor Effect and Minimize the Rhythm Disturbance Effect

Akagı

Ushinohama

Ikesue

et al. 2003

J Pharmacol Exp Ther

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The influence of dosing time on the antitumor effect and the rhythm disturbance effect of melatonin (MLT) was investigated in ICR male mice under a light/dark (12:12) cycle. In tumorbearing mice, the antitumor effect of MLT (1 mg/kg intraperitoneal) was most effective in the dark phase; and the rhythm disturbance effect of MLT on the locomotor activity was more serious in the light phase than in the dark phase. The antitumor effect and the rhythm disturbance effect of MLT increased when the specific binding of MLT receptor in target tissues, tumor or suprachiasmatic nucleus, increased and they decreased when the level decreased. Furthermore, because luzindole, an MT 1 and MT 2 blocker, caused the antitumor effect or rhythm disturbance effect of MLT to decrease, it is suggested that the time-dependent change of the pharmacological effects of MLT were influenced by that of MLT receptor(s) function. On the other hand, there was no significant dosing time-dependent change of MLT concentration in tumor or brain after injection. Thus, the pharmacokinetic factor does not seem to contribute to the dosing time-dependent effect of MLT. These results suggest that by choosing the most suitable dosing time for MLT, the efficacy of the drug can be increased, and the toxicity of the drug can be decreased in certain experimental and clinical situations.

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“…Melatonin receptors are detectable in T helper cells, lymphocytes, granulocytes, mast cells and monocytes/macrophages [64][65][66][67][68]. On the other hand, bone marrow cells and the mast cell line RBL-2H3 are able to synthesize melatonin [68,69].…”

Section: Melatonin In Testicular Immune Cellsmentioning

confidence: 99%

Local Actions of Melatonin in Somatic Cells of the Testis

Frungieri¹,

Calandra²,

Rossi³

2017

Preprint

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Environmental darkness signal is transferred from the retina to the pineal gland triggering melatonin secretion. Melatonin influences the synthesis and release of the hypothalamic GnRH and the adenohypophyseal gonadotropin hormones and therefore, regulates testicular function in photoperiodic species.Besides the brain, direct actions of melatonin at the testicular level have also been Peer-reviewed version available at Int. J. Mol. Sci. 2017, 18, , 1170 doi:10.3390/ijms18061170 2 of 41 protective effects against oxidative stress in testicular mast cells. These data pinpoints melatonin as a key player in the regulation of testicular physiology (i.e. steroidogenesis, spermatogenesis) mostly in seasonal breeders. More importantly, melatonin is also involved in the modulation of testicular inflammatory and oxidant/anti-oxidant states in patients with idiopathic infertility.

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Immunomodulatory role of melatonin: specific binding sites in human and rodent lymphoid cells

Cited by 137 publications

References 55 publications

Differential Effects of Fluvoxamine and Other Antidepressants on the Biotransformation of Melatonin

Differential Effects of Fluvoxamine and Other Antidepressants on the Biotransformation of Melatonin

Chronopharmacology of Melatonin in Mice to Maximize the Antitumor Effect and Minimize the Rhythm Disturbance Effect

Local Actions of Melatonin in Somatic Cells of the Testis

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