Melatonin receptors: Localization, molecular pharmacology and physiological significance

Morgan, Peter J.; Barrett, Perry; Howell, H. E.; Helliwell, Rachel J. A.

doi:10.1016/0197-0186(94)90100-7

Cited by 571 publications

(397 citation statements)

References 222 publications

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“…The search for biological substrates of annual timekeeping mechanisms has been largely restricted to mammals and focused on neural structures that might logically function as targets of melatonin action. In fact, the distribution of tissues that exhibit melatonin binding and receptor expression is highly species specific; the pars tuberalis (PT) of the pituitary gland is thought to be the only melatonin target tissue common to all mammals (Bittman 1993;Morgan et al 1994). Melatonin implants directed at various targets (including the anterior hypothalamus, SCN, nucleus reuniens, paraventricular nucleus of the thalamus or MBH) in sheep, Siberian hamsters or white-footed mice induce seasonal changes in various traits (Glass & Lynch 1982;Dowell & Lynch 1987;Badura & Goldman 1992;Lincoln & Maeda 1992;Malpaux et al 1998;.…”

Section: On the Location Of Interval Timers And Circannual Clocksmentioning

confidence: 99%

“…Melatonin is believed to act directly on PT cells to regulate photoperiodic changes in prolactin secretion (Lincoln & Clarke 1994); high melatonin receptor binding is seen in the PT of several species, whereas little to no binding is found in the pars distalis of adult sheep, Siberian hamsters, Syrian hamsters, rats and mice (Bittman & Weaver 1990;Morgan et al 1994). Current evidence suggests that melatonin-sensitive cells in the PT secrete a prolactin releasing factor ('tuberalin') that acts in a paracrine fashion to stimulate lactotrophs in the pars distalis (reviewed in Johnston 2004).…”

Section: On the Location Of Interval Timers And Circannual Clocksmentioning

confidence: 99%

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Tracking the seasons: the internal calendars of vertebrates

Paul

Zucker

Schwartz

2007

Phil. Trans. R. Soc. B

173

152

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Animals have evolved many season-specific behavioural and physiological adaptations that allow them to both cope with and exploit the cyclic annual environment. Two classes of endogenous annual timekeeping mechanisms enable animals to track, anticipate and prepare for the seasons: a timer that measures an interval of several months and a clock that oscillates with a period of approximately a year. Here, we discuss the basic properties and biological substrates of these timekeeping mechanisms, as well as their reliance on, and encoding of environmental cues to accurately time seasonal events. While the separate classification of interval timers and circannual clocks has elucidated important differences in their underlying properties, comparative physiological investigations, especially those regarding seasonal prolactin secretions, hint at the possibility of common substrates.Keywords: seasonality; photoperiodism; circannual; interval timers While the Earth remaineth, seedtime and harvest, and cold and heat, and summer and winter, and day and night shall not cease.Genesis 8: 22, King James Version (1611) As the Earth makes its yearly orbit around the Sun, the planet's 23.58 axial tilt leads to the cyclical environmental changes that we call the seasons. Recurrent challenges to the survival of organisms and their offspring arise with the dawning of each new season, and animals have evolved seasonally induced changes in phenotype that adapt them to these predictable events. For example, in many temperate environments, winter is generally characterized by severe decreases in ambient temperature and food availability, leading to increased energetic demands at a time when resources are diminished. Because energy requirements of female mammals typically increase markedly during lactation (Bronson 1989) and newly weaned offspring are particularly vulnerable to environmental perturbations (Hill 1992), raising offspring during this time of year is often futile. Thus, many temperate species have evolved winter-specific behaviours and physiology to conserve energy (e.g. hibernation, a more insulative pelage, huddling) or provide for escape (e.g. migration). Many species also increase the chances of offspring survival by timing their mating behaviours so that parturition occurs during energetically favourable times of year.

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Section: On the Location Of Interval Timers And Circannual Clocksmentioning

confidence: 99%

Section: On the Location Of Interval Timers And Circannual Clocksmentioning

confidence: 99%

Tracking the seasons: the internal calendars of vertebrates

Paul

Zucker

Schwartz

2007

Phil. Trans. R. Soc. B

173

152

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“…Several studies suggest that melatonin exerts its potent biological effects through specific receptors (Krause and Dubocovich, 1991;Morgan et al, 1994). Some years ago, with the development of the biologically active radioiodinated agonist 2-[ 125 I]-labelled melatonin (Vakkuri et al, 1984), high-affinity melatonin binding sites were convincingly identified in discrete brain regions and in chicken and rabbit retina by radioreceptor and autoradiographic techniques (Vanecek et al, 1987;Dubocovich, 1988a;Morgan and Williams, 1989).…”

mentioning

confidence: 99%

“…High-affinity binding sites have been detected in assays with crude membrane homogenates or in vitro autoradiography, in several tissues and organs (Morgan et al, 1994). Daily variation in 2-[ 125 I]-melatonin binding sites in the golden hamster retina (Faillace et al, 1995) has been reported.…”

mentioning

confidence: 99%

Daily morphological variations in the viscacha (Lagostomus maximus maximus) retina. Probable local modulatory action of melatonin

Calderón¹,

Mohamed²,

Muñoz³

et al. 2002

Anat. Rec.

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Given that the local melatonin levels exhibit rhythmic daily changes in the retina of the viscacha, we considered it important to study the likely daily variations in morphology and specific 2-[ 125 I]-iodomelatonin binding in retinas from this rodent and to correlate these putative changes with local indole levels. Adult animals of both sexes were captured in their habitat and were kept under a natural photoperiod. For light and electron microscopic studies the viscachas were sacrificed by decapitation at 08:00, 16:00, and 24:00 hr. A computer-assisted image analysis system was used to measure the thickness of the complete retina, the photoreceptor layer, the rod outer and inner segments, and the outer nuclear layer. The daily variation in 2-[ 125 I]-iodomelatonin binding sites was followed during a 24-hr light-dark cycle, the animals being sacrificed at six time points. The parameters studied showed significant variations throughout the 24-hr period. Maximal specific binding, lysosomal content in the pigment epithelium, and photoreceptor layer outer segment thicknesses were observed at 24:00 hr. Close contact between photoreceptor membranes and microvilli of the pigment epithelium was observed at 08:00 and 16:00 hr. Moreover, the minimal outer segment thickness at 16:00 hr was accompanied by a scarcity of dense bodies, such as lysosomes, a maximum dispersion of melanin pigment granules, and a minimum density of radioligand binding sites. Therefore, in the retina of the viscacha, we suggest that the interaction between melatonin and specific sites could be one of the factors or causes that participate in the regulation of the daily morphological changes observed in viscacha.

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“…Melatonin, thus, acts as a neuroendocrine transducer of circadian and seasonal photoperiodic information. In mammals, the physiological functions of melatonin are, among other mechanisms, regulation of the circadian clock in the hypothalamic suprachiasmatic nucleus (SCN), seasonal reproduction, and inhibition of dopamine release from the retina (Morgan et al 1994;Vanecek 1998). Experiments with pinealectomized animals demonstrated that melatonin also plays a role in energy expenditure, body mass regulation, and insulin peripheral action and secretion (Margraf and Lynch 1993;Lima et al 1998;La Fleur et al 1999;Picinato et al 2002).…”

mentioning

confidence: 99%

In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus

Anhê

Caperuto

Pereira-da-Silva

et al. 2004

Journal of Neurochemistry

106

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Melatonin is the pineal hormone that acts via a pertussis toxinsensitive G-protein to inhibit adenylate cyclase. However, the intracellular signalling effects of melatonin are not completely understood. Melatonin receptors are mainly present in the suprachiasmatic nucleus (SCN) and pars tuberalis of both humans and rats. The SCN directly controls, amongst other mechanisms, the circadian rhythm of plasma glucose concentration. In this study, using immunoprecipitation and immunoblotting, we show that melatonin induces rapid tyrosine phosphorylation and activation of the insulin receptor b-subunit tyrosine kinase (IR) in the rat hypothalamic suprachiasmatic region. Upon IR activation, tyrosine phosphorylation of IRS-1 was detected. In addition, melatonin induced IRS-1/PI(3)-kinase and IRS-1/SHP-2 associations and downstream AKT serine phosphorylation and MAPK (mitogen-activated protein kinase) phosphorylation, respectively. These results not only indicate a new signal transduction pathway for melatonin, but also a potential cross-talk between melatonin and insulin.

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Melatonin receptors: Localization, molecular pharmacology and physiological significance

Cited by 571 publications

References 222 publications

Tracking the seasons: the internal calendars of vertebrates

Tracking the seasons: the internal calendars of vertebrates

Daily morphological variations in the viscacha (Lagostomus maximus maximus) retina. Probable local modulatory action of melatonin

In vivo activation of insulin receptor tyrosine kinase by melatonin in the rat hypothalamus

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