Both Pertussis Toxin‐Sensitive and Insensitive G‐Proteins Link Melatonin Receptor to Inhibition of Adenylate Cyclase in the Ovine Pars Tuberalis

Morgan, Peter J.; Davidson, Gary; Lawson, Wilfred; Barrett, Perry

doi:10.1111/j.1365-2826.1990.tb00639.x

Cited by 85 publications

(61 citation statements)

References 21 publications

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“…More importantly, PTX-insensitive G proteins appear to link melatonin receptors to inhibition of adenylyl cyclase in the ovine pars tuberalis [21].…”

Section: Resultsmentioning

confidence: 99%

Stimulation of cAMP accumulation by the cloned Xenopus melatonin receptor through G_i and G_z proteins

1995

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The Xenopus melatonin receptor was expressed in human embryonic kidney 293 cells and assayed for cAMP accumulation. In transfected 293 cells expressing the melatonin receptor, melatonin dose-dependently inhibited the endogenous adenylyi cyclases. In contrast, melatonin stimulated the accumulation of cAMP in cells co-expressing the type II adenylyl cyclase. Both the inhibitory and stimulatory responses to melatonin were mediated via Gi-like proteins as they were blocked by pertussis toxin. Upon co-transfection with the oz subunit of G~, the ability of melatonin to regulate both type H and the endogenous adenylyl cyclases became refractory to pertussis toxin, indicating that the melatonin receptor can also couple to Gz. However, other pertussis toxin-insensitive G proteins such as Gq, G~2 and G13 were unable to interact with the melatonin receptor.

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“…More importantly, PTX-insensitive G proteins appear to link melatonin receptors to inhibition of adenylyl cyclase in the ovine pars tuberalis [21].…”

Section: Resultsmentioning

confidence: 99%

Stimulation of cAMP accumulation by the cloned Xenopus melatonin receptor through G_i and G_z proteins

1995

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“…Thus, melatonin and its analogs inhibit dopamine-stimulated CAMP accumulation by activating melatonin receptors similar to those described pre- viously using other functional or binding assays. Furthermore, the inhibitory effect of melatonin on dopamine-stimulated CAMP accumulation was blocked by pretreatment with pertussis toxin, which also attenuates the inhibition by melatonin of forskolin-stimulated CAMP accumulation in retinal cells (Iuvone and Gan, 1994), brain (Niles et al, 1991), and pars tuberalis (Morgan et al, 1990). Thus, we suggest that melatonin stimulates receptors located on neurons that also contain Dl dopamine receptors, and that the melatonin receptors activate a G,-like guanyl nucleotide binding protein that inhibits the effect of G, activation by Dl dopamine receptor stimulation.…”

Section: Discussionmentioning

confidence: 99%

Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

Iuvone

Gan

1995

J. Neurosci.

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The possible interaction of melatonin receptors and D1 dopamine receptors was investigated in neural cells prepared from embryonic day 8 chick retinas and cultured for 6 d. Dopamine stimulated cAMP accumulation in cultured retinal cells. This effect of dopamine was antagonized by addition of dopamine receptor antagonists (haloperidol and SCH23390) or melatonin receptor agonists (melatonin, 2- iodomelatonin, and 6-chloromelatonin). The inhibition of dopamine- stimulated cAMP accumulation by melatonin was concentration dependent, with half-maximal inhibition at approximately 160 pM. Melatonin inhibited the effect of dopamine at all dopamine concentrations, suppressing the maximal response to the neurotransmitter by approximately 70%. Melatonin also inhibited the stimulation of cAMP accumulation by SKF 82958, a selective D1 dopamine receptor agonist. Pretreatment of cultures with pertussis toxin had no significant effect on dopamine-stimulated cAMP accumulation, but inhibited the response to melatonin. In contrast to its effect on cAMP accumulation, melatonin had no effect on dopamine-stimulated inositol phosphate accumulation. These results suggest that melatonin receptors are coupled to dopamine receptor-regulated adenylate cyclase via an inhibitory G protein, and demonstrate another mechanism, in addition to inhibition of dopamine release, through which melatonin can modulate dopaminergic neurotransmission.

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“…A number of studies have investigated the signal transduction mechanisms in tissues associated with the hypothalamicpituitary-gonadal axis. At the level of the pituitary, melatonin inhibits adenylate cyclase through both PTX (pertussis toxin)-sensitive and PTX-insensitive G-proteins in ovine pars tuberalis cells (5,6). Melatonin also inhibits gonadotropin-releasing hormone (GnRH)-induced increases in cAMP, diacylglycerol, [Ca 2ϩ ] i , and c-Fos in neonatal rat gonadotrophs (7,8).…”

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confidence: 99%

Melatonin Receptor Activation Regulates GnRH Gene Expression and Secretion in GT1–7 GnRH Neurons

Roy¹,

Belsham²

2002

Journal of Biological Chemistry

129

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Melatonin plays a significant role in the control of the hypothalamic-pituitary-gonadal axis. Using the GT1-7 cell line, an in vitro model of GnRH-secreting neurons of the hypothalamus, we examined the potential signal transduction pathways activated by melatonin directly at the level of the GT1-7 neuron. We found that melatonin inhibits forskolin-stimulated adenosine 3-, 5-cyclic monophosphate accumulation in GT1-7 cells through an inhibitory G protein. Melatonin induced protein kinase C activity by 1.65-fold over basal levels, increased the phosphorylation of extracellular signal-regulated kinase 1 and 2 proteins, and activated c-fos and junB mRNA expression in GT1-7 cells. Using the protein kinase A inhibitor H-89, the protein kinase C inhibitor bisindolylmaleimide, and the mitogen-activated protein kinase kinase inhibitor PD98059, we found that the melatonin-mediated cyclical regulation of GnRH mRNA expression may involve the protein kinase C and the extracellular signal-regulated kinase 1 and 2 pathways, but not the protein kinase A pathway. We found that melatonin suppresses GnRH secretion by ϳ45% in the GT1-7 neurons. However, in the presence of the inhibitors H-89, bisindolylmaleimide, and PD98059 melatonin was unable to suppress GnRH secretion. These results provide insights into the potential signal transduction mechanisms involved in the control of GnRH gene expression and secretion by melatonin.

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Both Pertussis Toxin‐Sensitive and Insensitive G‐Proteins Link Melatonin Receptor to Inhibition of Adenylate Cyclase in the Ovine Pars Tuberalis

Cited by 85 publications

References 21 publications

Stimulation of cAMP accumulation by the cloned Xenopus melatonin receptor through G_i and G_z proteins

Stimulation of cAMP accumulation by the cloned Xenopus melatonin receptor through G_i and G_z proteins

Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

Melatonin Receptor Activation Regulates GnRH Gene Expression and Secretion in GT1–7 GnRH Neurons

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Both Pertussis Toxin‐Sensitive and Insensitive G‐Proteins Link Melatonin Receptor to Inhibition of Adenylate Cyclase in the Ovine Pars Tuberalis

Cited by 85 publications

References 21 publications

Stimulation of cAMP accumulation by the cloned Xenopus melatonin receptor through Gi and Gz proteins

Stimulation of cAMP accumulation by the cloned Xenopus melatonin receptor through Gi and Gz proteins

Functional interaction of melatonin receptors and D1 dopamine receptors in cultured chick retinal neurons

Melatonin Receptor Activation Regulates GnRH Gene Expression and Secretion in GT1–7 GnRH Neurons

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Stimulation of cAMP accumulation by the cloned Xenopus melatonin receptor through G_i and G_z proteins

Stimulation of cAMP accumulation by the cloned Xenopus melatonin receptor through G_i and G_z proteins