Picomolar-affinity binding and inhibition of adenylate cyclase activity by melatonin in syrian hamster hypothalamus

Niles, Lennard P.; Hashemi, Fereshteh

doi:10.1007/bf00712848

Cited by 30 publications

(9 citation statements)

References 17 publications

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“…Indeed, the MBH seems to be a target for melatonin, as reported in the Introduction (9,11,35). It has been suggested that the inhibitory effect of melatonin on forskolin-stimulated adenylate-cyclase activity in hypothalamic homogenates could be mediated by melatonin binding sites (36).…”

Section: Discussionmentioning

confidence: 91%

Effect of Melatonin on the Release of Gonadotropin‐Releasing Hormone and Cyclic AMP from the Rat Hypothalamus: an in vitro Study

Messager

Caillol

Rossano

et al. 1996

J Neuroendocrinology

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Using an in vitro static incubation system of adult male rat hypothalami, we have studied the effect of melatonin on the release of gonadotropin-releasing hormone (GnRH) and cyclic adenosine monophosphate (cAMP). Mediobasal hypothalamus (MBH) and preoptic area (POA) were incubated separately in Minimum Essential Medium (MEM) for 6 h. The release of GnRH was measured by radioimmuno-assay in the incubation medium sampled every 7.5 min. In the MBH and POA incubation medium, the mean amount of GnRH released was 8.9 +/- 1.1 and 3.4 +/- 0.6 pg GnRH/7.5 min, respectively (P < 0.01). The mean number of GnRH pulses under basal conditions was 2 +/- 0.3 per 2 h in the MBH and 1.6 +/- 0.3 per 2 h in the POA (P > 0.05). Melatonin (10(-8) M) did not alter the release of GnRH in the presence or absence of forskolin (10(-4) M). Melatonin, which was without effect on basal cAMP, inhibited forskolin-stimulated cAMP accumulation in the medium by 50% in the MBH and 40% in the POA. These results suggest that in our incubation system, melatonin does not modify GnRH release, but probably acts through the melatonin binding sites located in the hypothalamus to inhibit forskolin-stimulated cAMP.

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Section: Discussionmentioning

confidence: 91%

Effect of Melatonin on the Release of Gonadotropin‐Releasing Hormone and Cyclic AMP from the Rat Hypothalamus: an in vitro Study

Messager

Caillol

Rossano

et al. 1996

J Neuroendocrinology

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“…As determined by cAMP direct immunoassay, the higher 2500 μ m melatonin dose was able to decrease cAMP concentration, and this effect was abolished by luzindole, which increased cAMP in the presence of melatonin but not when administered alone. It has been shown that melatonin inhibits activity of adenylyl cyclase in a dose‐dependent manner [44]. Previous studies have indicated that the coupling of both MT1 and MT2 receptors seem to be necessary to inhibit adenyl cyclase when melatonin is administered at low doses [45].…”

Section: Discussionmentioning

confidence: 99%

Melatonin modulation of intracellular signaling pathways in hepatocarcinoma HepG2 cell line: role of the MT1 receptor

Carbajo-Pescador

García‐Palomo

Martín-Renedo

et al. 2011

Journal of Pineal Research

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Melatonin reduces proliferation in many different cancer cell lines. However, studies on the oncostatic effects of melatonin in hepatocarcinoma are limited. We have previously demonstrated that melatonin administration induces cycle arrest, apoptosis, and changes in the expression of its specific receptors in HepG2 human hepatocarcinoma cells. In this study, we used the receptor antagonist luzindole to assess the contribution of MT1 melatonin membrane receptor to melatonin effects on cell viability, mitogen-activated protein kinase (MAPKs) activation, and cAMP levels. Additionally, effects of MT1 inhibition on mRNA levels of cytosolic quinone reductase type-2 (NQO2) receptor and nuclear retinoic acid-related orphan receptor alpha (RORα) were tested. Melatonin, at 1000 and 2500 μm, significantly reduced cell viability. Pre-incubation with luzindole partially inhibited the effects of melatonin on cell viability. Melatonin at 2500 μm significantly reduced cAMP levels, and this effect was partially blocked by luzindole. Both melatonin concentrations increased the expression of phosphorylated p38, ERK, and JNK. ERK activation was completely abolished in the presence of luzindole. NQO2 but not RORα mRNA level significantly increased in luzindole-treated cells. Results obtained provide evidence that the melatonin effects on cell viability and proliferation in HepG2 cells are partially mediated through the MT1 membrane receptor, which seems to be related also with melatonin modulation of cAMP and ERK activation. This study also highlights a possible interplay between MT1 and NQO2 melatonin receptors in liver cancer cells.

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“…Melatonin also has long established inhibitory effects on the adenylate cyclase -cyclic AMP pathway (Niles and Hashemi, 1990;Niles et al, 1991;Vanecek, 1998), with consequent suppression of cAMP response element binding protein (CREB) phosphorylation (Kopp et al, 1997;von Gall et al, 2000). However, some of melatonin's actions are receptor-independent, involving interactions with intracellular targets including calmodulin, protein kinase C and nuclear receptors such as the retinoid Z receptor/retinoid acid receptor-related orphan receptor (RZR/ROR) (Agez et al, 2007;Carlberg, 2000;Luchetti et al, 2010;Soto-Vega et al, 2004).…”

Section: Introductionmentioning

confidence: 98%

Epigenetic mechanisms of melatonin action in human SH-SY5Y neuroblastoma cells

Pan

Niles

2015

Molecular and Cellular Endocrinology

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Picomolar-affinity binding and inhibition of adenylate cyclase activity by melatonin in syrian hamster hypothalamus

Cited by 30 publications

References 17 publications

Effect of Melatonin on the Release of Gonadotropin‐Releasing Hormone and Cyclic AMP from the Rat Hypothalamus: an in vitro Study

Effect of Melatonin on the Release of Gonadotropin‐Releasing Hormone and Cyclic AMP from the Rat Hypothalamus: an in vitro Study

Melatonin modulation of intracellular signaling pathways in hepatocarcinoma HepG2 cell line: role of the MT1 receptor

Epigenetic mechanisms of melatonin action in human SH-SY5Y neuroblastoma cells

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