Melatonin generates an outward potassium current in rat suprachiasmatic nucleus neurones in vitro independent of their circadian rhythm

Top, M. van den; Buijs, Ruud M.; Delagrange, Philippe; Spanswick, David; Hermes, Michael

doi:10.1016/s0306-4522(01)00346-3

Cited by 80 publications

(67 citation statements)

References 42 publications

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“…Ample experimental evidence indicates that K + channels may serve as effectors for melatonin signaling. In SCN neurons, melatonin induces an outward potassium current that is sensitive to PTX but independent of cAMP levels and PLC activity [98]. Similar findings have been observed in rat cerebellar granule cells [99].…”

Section: Potassium Channelssupporting

confidence: 67%

G Protein-Linked Effector and Second Messenger Systems Involved in Melatonin Signal Transduction

New

Tsim

Wong³

2003

Neurosignals

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The isolation and characterization of multiple melatonin receptors in a wide range of tissues and cells signifies the functional diversity of melatonin. In different cellular environments, melatonin can regulate distinct second messengers or even positively or negatively regulate the same signal transduction pathway. The capacity by which melatonin receptors modulate the activities of various effector molecules is determined by the complement of signaling components present in any particular cell type. The specific interactions between many signaling molecules have been discerned in an increasing number of cellular systems and this information is being used to explain the physiological actions of melatonin. This review will attempt to summarize recent research by many groups that has revealed numerous subtleties of the melatonin-coupled signaling pathways.

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Section: Potassium Channelssupporting

confidence: 67%

G Protein-Linked Effector and Second Messenger Systems Involved in Melatonin Signal Transduction

New

Tsim

Wong³

2003

Neurosignals

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“…This effect could be mediated via an immediate inhibition of SCN-neuronal activity inducing a state resembling nocturnal SCN output. 16,17,38 However, daytime melatonin intake results in sleepiness and hypothermia during the day 39 and should thus be avoided. On the contrary, repeated nighttime melatonin supports the endogenous melatonin rhythm, improving circadian rhythmicity.…”

Section: Discussionmentioning

confidence: 99%

Daily Nighttime Melatonin Reduces Blood Pressure in Male Patients With Essential Hypertension

et al. 2004

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Abstract-Patients with essential hypertension have disturbed autonomic cardiovascular regulation and circadian pacemaker function. Recently, the biological clock was shown to be involved in autonomic cardiovascular regulation. Our objective was to determine whether enhancement of the functioning of the biological clock by repeated nighttime melatonin intake might reduce ambulatory blood pressure in patients with essential hypertension. We conducted a randomized, double-blind, placebo-controlled, crossover trial in 16 men with untreated essential hypertension to investigate the influence of acute (single) and repeated (daily for 3 weeks) oral melatonin (2.5 mg) intake 1 hour before sleep on 24-hour ambulatory blood pressure and actigraphic estimates of sleep quality. Repeated melatonin intake reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg, respectively. The treatment did not affect heart rate. The day-night amplitudes of the rhythms in systolic and diastolic blood pressures were increased by 15% and 25%, respectively. A single dose of melatonin had no effect on blood pressure. Repeated (but not acute) melatonin also improved sleep. Improvements in blood pressure and sleep were statistically unrelated. In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure. Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake. The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension. Key Words: blood pressure monitoring Ⅲ circadian rhythm Ⅲ hormones Ⅲ human Ⅲ hypertension T he endogenous circadian pacemaker, located in the suprachiasmatic nucleus (SCN), imposes 24-hour biological rhythms by endocrine and autonomic mechanisms. 1 For example, the circadian rhythm in adrenal cortex activity is regulated via an endocrine and a sympathetic route, 2,3 that of heart and liver via sympathetic and parasympathetic control, 4 -6 and of the pineal gland via the sympathetic nervous system. 7 Thus, the SCN promotes adaptation to the rest and activity periods by regulating, for example, the morning increase in cortisol, heart rate, and glucose, and the evening increase in melatonin.Evidence for disturbed circadian pacemaker function in essential hypertension is accumulating. Patients with hypertension show blunted day-night rhythms in sympathetic and parasympathetic heart tone. 8,9 Patients with coronary heart disease, a major complication of chronic hypertension, show a blunted day-night rhythm in vasodilatation 10 and suppressed nighttime melatonin levels. 11 We demonstrated recently that in comparison with normotensive subjects, the levels of three important SCNneurotransmitters are reduced by more than 50% in patients with essential hypertension, 12 corroborating its functional impairment. Furthermore, we provided anatomical support for a changed SCN output to the symp...

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“…For example, in vivo, subcutaneous Mel injections in rats inhibit the uptake of the metabolic marker 2-deoxy[ 14 C]glucose within the SCN during the late subjective day but have no effect during the early subjective day or night (Cassone et al 1988). Superfusion or iontophoresis of Mel on rat hypothalamic slice preparation in vitro inhibits SCN electrical activity (Shibata et al 1989;Stehle et al 1989;van den Top et al 2001) and, when administered late in the subjective day, phase shift the firing rate of SCN neurons (rat and mouse) (Gillette and McArthur 1996). It has also been observed that SCNlesioned hamsters whose rhythmicity had been restored with fetal hypothalamic grafts are entrained by daily Mel injections, and Mel is known to accelerate the reentrainment of circadian rhythms (locomotor activity as well as N-acetyltransferase, AANAT, activity) in rats subjected to a shift in the LD cycle (Redman and Armstrong 1988;Humlova and Illnerova 1989).…”

Section: Suprachiasmatic Nuclei and Melatonin Receptorsmentioning

confidence: 99%

The chronobiotic properties of melatonin

Pévet¹,

Bothorel²,

Slotten³

et al. 2002

Cell Tissue Res

137

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In mammals, the exact role of melatonin (Mel) in the circadian timing system remains to be determined. However, exogenously administered Mel, as reported in the present mini-review, has been shown to affect the circadian clock. The sites and mechanisms of action involved in this "chronobiotic" effect of Mel have begun to be characterized. The suprachiasmatic nuclei (SCN) appear to be an important site for the entrainment effect of Mel and the presence of Mel receptors appears to be a prerequisite. However, the pharmacological dose of Mel needed to entrain circadian rhythms means that very probably other sites and mechanisms also play a role.

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Melatonin generates an outward potassium current in rat suprachiasmatic nucleus neurones in vitro independent of their circadian rhythm

Cited by 80 publications

References 42 publications

G Protein-Linked Effector and Second Messenger Systems Involved in Melatonin Signal Transduction

G Protein-Linked Effector and Second Messenger Systems Involved in Melatonin Signal Transduction

Daily Nighttime Melatonin Reduces Blood Pressure in Male Patients With Essential Hypertension

The chronobiotic properties of melatonin

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