Involvement of alpha- and beta-adrenergic receptors in the regulation of rat pineal N-acetyltransferase activity during development

Rubio, A.E.

doi:10.1210/en.132.1.393

Cited by 12 publications

(4 citation statements)

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“…In NAT experiments, we used pineal glands of isoproterenol-treated rats as a positive control and used noninjected animals as positive control of HIOMT activity. Isoproterenol is a β-adrenergic agonist that typically activates pineal NAT (28). The specific activity of NAT in lymphocytes was similar to that obtained in the pineal gland of rats injected with isoproterenol, whereas HIOMT activity was higher than in pineal glands.…”

Section: Presence Of Two Key Enzymes Involved In Melatonin Synthesis supporting

confidence: 69%

Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance

Carrillo-Vico¹,

Calvo²,

Abreu³

et al. 2004

FASEB j.

398

287

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It has been historically assumed that the pineal gland is the major source of melatonin (N-acetyl-5-methoxytryptamine) in vertebrates. Melatonin plays a central role in fine-tuning circadian rhythms in vertebrate physiology. In addition, melatonin shows a remarkable functional versatility exhibiting antioxidant, oncostatic, antiaging, and immunomodulatory properties. Melatonin has been identified in a wide range of organisms from bacteria to human beings. Its biosynthesis from tryptophan involves four well-defined intracellular steps catalyzed by tryptophan hydroxylase, aromatic amino acid decarboxylase, serotonin-N-acetyltransferase, and hydroxyindole-O-methyltransferase. Here, for the first time, we document that both resting and phytohemagglutinin-stimulated human lymphocytes synthesize and release large amounts of melatonin, with the melatonin concentration in the medium increasing up to five times the nocturnal physiological levels in human serum. Moreover, we show that the necessary machinery to synthesize melatonin is present in human lymphocytes. Furthermore, melatonin released to the culture medium is synthesized in the cells, because blocking the enzymes required for its biosynthesis or inhibiting protein synthesis in general produced a significant reduction in melatonin release. Moreover, this inhibition caused a decrease in IL-2 production, which was restored by adding exogenous melatonin. These findings indicate that in addition to pineal gland, human lymphoid cells are an important physiological source of melatonin and that this melatonin could be involved in the regulation of the human immune system, possibly by acting as an intracrine, autocrine, and/or paracrine substance.

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Section: Presence Of Two Key Enzymes Involved In Melatonin Synthesis supporting

confidence: 69%

Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance

Carrillo-Vico¹,

Calvo²,

Abreu³

et al. 2004

FASEB j.

398

287

View full text Add to dashboard Cite

show abstract

“…Furthermore, and in contrast to previous studies (28,29), we show that neonate adrenergic receptors are mature for a/b selectivity because the a-adrenergic antagonist prazosin does not affect Aa-nat mRNA expression while b-adrenergic antagonist inhibits Aa-nat mRNA expression, as reported in the adult (8).…”

Section: Discussioncontrasting

confidence: 99%

Syrian Hamster and Rat Display Developmental Differences in the Regulation of Pineal Arylalkylamine N‐Acetyltransferase

Garidou¹,

Ribelayga²,

Pévet³

et al. 2002

J Neuroendocrinology

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In the Syrian hamster, the role of noradrenaline in the regulation of melatonin synthesis is less clear than in the rat. During pineal ontogenesis in the rat, noradrenaline is the major transmitter involved in the onset of melatonin synthesis and melatonin rhythm. We analysed the involvement of noradrenaline in the ontogenesis of melatonin synthesis in the Syrian hamster and compared it with that of the rat. We followed the developmental profile of melatonin content in parallel with those of mRNA expression and activity of AA-NAT, the melatonin rhythm-generating enzyme. In addition, we tested the effect of noradrenergic drugs at early steps of pineal ontogenesis. In the Syrian hamster, the night-time Aa-nat mRNA, first detected 3 days after birth, increases progressively up to a maximum reached at 30 days of age and then decreases significantly towards adulthood. The daytime level of Aa-nat mRNA remains always low. A significant day/night rhythm appears 10 days after birth, is maximal (200-fold nocturnal increase) 30 days after birth and decreases slowly towards adulthood. Ontogenesis of the AA-NAT activity rhythm is similar, although with a much lower amplitude of day/night variations (four-fold). The developmental pattern of melatonin content is similar to that of AA-NAT and could be correlated with the appearance of sympathetic innervation in the pineal gland. However, neither alpha- nor beta-adrenergic antagonists inhibit the night-time Aa-nat mRNA transcription in the 9-day-old Syrian hamster, in contrast to what is observed in the adult. For comparison, the beta-adrenergic antagonist propranolol inhibits Aa-nat gene expression in 2-day-old rat. These results show that both species are different in the regulation of the appearance of melatonin synthesis and that Syrian hamster is peculiar from birth in term of noradrenaline involvement in the activation of melatonin synthesis.

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“…Pineal glands of isoproterenol-treated rats were used as a positive control. Isoproterenol is a b-adrenergic agonist which typically activates pineal NAT (Rubio et al, 1993).…”

Section: Presence Of Two Key Enzymes Involved In Melatonin Synthesis mentioning

confidence: 99%

Melatonin synthesized by Jurkat human leukemic T cell line is implicated in IL‐2 production

Lardone

Carrillo-Vico

Naranjo

et al. 2005

Journal Cellular Physiology

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Human lymphocytes have recently been described as an important physiological source of melatonin (N-acetyl-5-methoxytryptamine), which could be involved in the regulation of the human immune system. On the other hand, stimulation of IL-2 production by exogenous melatonin has been shown in the Jurkat human lymphocytic cell line. Furthermore, both melatonin membrane and nuclear receptors are present in these cells. In this study, we show that the necessary machinery to synthesize melatonin is present and active in resting and stimulated Jurkat cells. Accordingly, we have found that cells synthesize and release melatonin in both conditions. Therefore, we investigated whether endogenous melatonin produced by Jurkat cells was involved in the regulation of IL-2 production. When melatonin membrane and nuclear receptors were blocked using specific antagonists, luzindole and CGP 55644, respectively, we found that IL-2 production decreased, and this drop was reverted by exogenous melatonin. Additionally, PHA activation of Jurkat cells changed the profile of melatonin nuclear receptor mRNA expression. A previous study showed that exogenous melatonin is able to counteract the decrease in IL-2 production caused by prostaglandin E2 (PGE2) in human lymphocytes via its membrane receptor. In our model, when we blocked the melatonin membrane receptor with luzindole, the inhibitory effect of PGE2 on IL-2 production was higher. Therefore, we have demonstrated the physiological role of endogenous melatonin in this cell line. These findings indicate that endogenous melatonin synthesized by human T cells would contribute to regulation of its own IL-2 production, acting as an intracrine, autocrine, and/or paracrine substance.

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Involvement of alpha- and beta-adrenergic receptors in the regulation of rat pineal N-acetyltransferase activity during development

Cited by 12 publications

References 0 publications

Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance

Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance

Syrian Hamster and Rat Display Developmental Differences in the Regulation of Pineal Arylalkylamine N‐Acetyltransferase

Melatonin synthesized by Jurkat human leukemic T cell line is implicated in IL‐2 production

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