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

Abstract

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.

Melatonin Modulates the GABAergic Response in Cultured Rat Hippocampal Neurons

“…Firstly, luzindole, a specific melatoninreceptor antagonist (31), could not block the melatonin's effects. In addition, it was previously demonstrated that the melatonin concentration needed to activate melatonin receptors is of the micromolar order (20,21,32). It was found in the present work, however, that the modulatory effects of melatonin were not observed at concentrations lower than 100 μM.…”

Molecular and functional characterization of a partial cDNA encoding a novel chicken brain melatonin receptor

“…No endogenous MLR activity was observed in cells only expressing D1 receptors and while 1/.tM forskolin stimulated the production of cAMP-100-fold over basal levels the addition of 100 nM ML resulted in an -30% decrease of forskolin stimulated cAMP accumulation in HEK-293 cells transiently expressing the cloned flcMLR (data not shown). Although it is unclear whether ML-and dopamine Dl-like receptors co-exist in the same neurons, evidence for functional ML and dopamine D1 receptor cross-talk regulating the activity of adenylate cyclase in cultured retinal cells has recently been documented [19,28]. The data on cloned receptors provide direct molecular evidence for the existence of functional ML-dopamine receptor interactions at the level of the single cell.…”

“…In the retina, ML inhibits dopamine synthesis and release [24] with a pharmacological profile and rank order of potency corresponding to the high-affinity ML~ receptor [25] found in either the rabbit retina or other neuronal and peripheral tissues from the same or different species ( [26,27] and see [2,13]). Moreover, in the retina, many opposing physiological and regulatory actions between dopamine and ML have been documented (see [28] and references therein). These interactions do not appear restricted to the retina, however, but may be evidenced as well in the hypothalamus and the pituitary gland where dopamine and ML regulate hormone release [29,30].…”

“…These interactions do not appear restricted to the retina, however, but may be evidenced as well in the hypothalamus and the pituitary gland where dopamine and ML regulate hormone release [29,30]. Although the molecular mechanism(s) by which these putative opposing interactions occur are still unknown, possible cross-talk between ML and dopamine D 1 receptor-mediated signal transduction events has been suggested [28].…”

P1‐091: The mt2 receptor stimulates axonogenesis and enhances synaptic transmission by activating akt signaling

“…33,44 Both loss of the MT2 receptor and a decrease in melatonin are highly correlated with Alzheimer's disease, 12,14,15 and the cellular protection of melatonin or MT2 receptor activation has been well clarified. 45,46 Moreover, dopamine, 47 estrogen, 48 thyroid hormone, 49 acetylcholine, 50 glutamate, 51 GABA, 52 or their receptors 53 can affect or crosstalk with the melatonin/MT2 receptor, and most of these molecules have an important role in axonogenesis or synapse formation. [54][55][56][57] It remains unclear whether and how melatonin/MT2 receptor signaling interacts with these hormone and neurotransmitter systems in the brain, but it is conceivable that activation of the MT2 receptor could be a practical strategy to regenerate renascent axons from dendrites on mature neurons for the treatment of neurological diseases such as AD.…”