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Melatonin Release (melatonin + release)
Selected AbstractsHypocretin (orexin) in the rat pineal gland: a central transmitter with effects on noradrenaline-induced release of melatoninEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2001Jens D. Mikkelsen Abstract Hypocretin-1 (HCRT-1) and hypocretin 2 (HCRT-2), also known as orexin-A and orexin-B, are two neuropeptides derived from the same precursor. Hypocretinergic neurons have been found exclusively in the hypothalamic dorsolateral area. These neurons are implicated in sleep and feeding through activation of specific G-protein-coupled orexin-1 and orexin-2 receptor (OR-R1 and OR-R2). The purpose of this study was to determine the existence of the HCRT peptides in the central input of the rat pineal gland. Further, OR-R1 and OR-R2 expression was determined in the pineal gland and the effect of HCRT-2 on melatonin synthesis and secretion was analysed in dissociated rat pinealocytes. A large contingent of HCRT-positive nerve fibres and terminals were observed in the epithalamus, many of which entered into the pineal parenchyma. A significant number of nerve fibres endowed with positive boutons were identified in the pineal stalk, though the number of positive fibres decreased along the extension of the stalk. So far, no positive fibres have been found in the superficial pineal gland. RT-PCR analysis revealed the expression of OR-R2 mRNA, whereas OR-R1-receptor mRNA was not detected. When tested alone, HCRT-2 had no effect on secretion of melatonin from cultured rat pinealocytes. However, HCRT-2 partially inhibited (by a maximum of 30%) the ,-adrenergic-induced melatonin secretion. The same effect was seen on activation of N-acetyltransferase activity. The distribution and the large number of HCRT-positive fibres together with the effect on noradrenaline-mediated melatonin release through specific receptors suggests that these peptides may be significant central transmitters in pineal function, probably mediating homeostatic signals to the pineal gland. [source] N-terminal residues regulate proteasomal degradation of AANATJOURNAL OF PINEAL RESEARCH, Issue 3 2010Zheping Huang Abstract:, Serotonin N -acetyltransferase (AANAT) catalyzes the conversion of serotonin to N -acetylserotonin, which is the immediate precursor for formation of melatonin. Although it is known that AANAT is degraded via the proteasomal proteolysis, detailed mechanisms are not defined. In this paper, we tested the in vivo role of proteasome inhibition on AANAT activity and melatonin release and examined the amino acid residues in AANAT that contribute to the proteasome degradation. We have shown that inhibition of proteasome activities in vivo in the intact pineal gland fails to prevent the light-induced suppression of melatonin secretion. Furthermore, in cell lines stably expressing AANAT, inhibition of proteasomal proteolysis, which resulted in a large accumulation of AANAT protein, similarly failed to increase AANAT enzyme activity proportional to the amount of proteins accumulated. Site-directed mutagenesis analysis of AANAT revealed that the AANAT degradation is independent of lysine and the two surface cysteine residues. Deletion analysis of N-terminus identified the second amino acid leucine (L2) as the key residue that contributes to the proteasomal proteolysis of AANAT protein. These results suggest that rat AANAT protein is degraded via the N-end rule pathway of proteasomal proteolysis and the leucine at the N-terminus appears to be the key residue recognized by N-end rule pathway. [source] How important is stimulation of ,-adrenoceptors for melatonin production in rat pineal glands?JOURNAL OF PINEAL RESEARCH, Issue 4 2002V. A. Tobin The objective of this study was to determine the role of , -adrenoceptors in melatonin production by rat pineal gland. Pineal glands were isolated from adult male rats and maintained in organ baths. The perfusate was sampled every 5 min, stored, and later assayed for melatonin. Exposure to norepinephrine (10 ,M) or the , -adrenoceptor agonist orciprenaline (2,10 ,M) increased the glands' production of melatonin. The time courses of melatonin production in response to these agonists were unaffected by the rats' pretreatment in vivo with the , -adrenoceptor antagonist prazosin (2 mg/kg i.p., three times). Rats that had had their superior cervical ganglia removed were primed with either orciprenaline (2 mg/kg i.p) or both orciprenaline and phenylephrine (1 mg/kg i.p) 1 hr before decapitation. Exposure of the pineal glands from these rats to orciprenaline evoked melatonin release that was similar in each group. These results lend weight to the suggestion that the marked potentiation by , -adrenoceptor agonists of the stimulation of cAMP and N-acetyltransferase (NAT) by , -adrenoceptor agonists, demonstrated most readily in cultured glands or dispersed rat pinealocytes, does not carry over into significant augmentation of melatonin production in intact pineal glands. [source] Bright light therapy in Parkinson's disease: A pilot studyMOVEMENT DISORDERS, Issue 10 2007Sebastian Paus MD Abstract Several observations suggest a beneficial effect of melatonin antagonism for Parkinson's disease (PD). Although bright light therapy (BLT) suppresses melatonin release and is an established treatment for depression and sleep disturbances, it has not been evaluated in PD. We examined effects of BLT on motor symptoms, depression, and sleep in PD in a randomized placebo-controlled double-blind study in 36 PD patients, using Parkinson's Disease Rating Scale (UPDRS) I,IV, Beck's Depression Inventory, and Epworth Sleepiness Scale. All patients received BLT for 15 days in the morning, 30 min daily. Illuminance was 7.500 lux in the active treatment group and 950 lux in the placebo group. Although group differences were small, BLT led to significant improvement of tremor, UPDRS I, II, and IV, and depression in the active treatment group but not in the placebo group. It was very well tolerated. Follow up studies in more advanced patient populations employing longer treatment durations are warranted. © 2007 Movement Disorder Society [source] Circadian proteomics of the mouse retinaPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 19 2007Takahiro Tsuji Abstract The circadian clock in the retina regulates a variety of physiological phenomena such as disc shedding and melatonin release. Although these events are critical for retinal functions, it is almost unknown how the circadian clock controls the physiological rhythmicity. To gain insight into the processes, we performed a proteomic analysis using 2-DE to find proteins whose levels show circadian changes. Among 415 retinal protein spots, 11 protein spots showed circadian rhythmicity in their intensities. We performed MALDI-TOF MS and NanoLC-MS/MS analyses and identified proteins contained in the 11 spots. The proteins were related to vesicular transport, calcium-binding, protein degradation, metabolism, RNA-binding, and protein foldings, suggesting the clock-regulation of neurotransmitter release, transportation of the membrane proteins, calcium-binding capability, and so on. We also found a rhythmic phosphorylation of N -ethylmaleimide-sensitive fusion protein and identified one of the amino acid residues modified by phosphorylation. These findings provide a new perspective on the relationship between the physiological functions of the retina and the circadian clock system. [source] Stereoselective effects of (R)- and (S)-carvedilol in humansCHIRALITY, Issue 7 2001Kurt Stoschitzky Abstract Carvedilol is currently used as the racemic mixture, (R,S)-carvedilol, consisting of equal amounts of (R)-carvedilol, an alpha-blocker, and (S)-carvedilol, an alpha- and beta-blocker, which have never been tested in their optically pure forms in human subjects. We performed a randomized, double-blind, placebo-controlled, crossover study in 12 healthy male volunteers. Subjects received single oral doses of 25 mg (R,S)-carvedilol, 12.5 mg (R)-carvedilol, 12.5 mg (S)-carvedilol, and placebo at 8 AM as well as at 8 PM. Exercise was performed at 11 AM, and heart rate and blood pressure were measured at rest and after 10 min of exercise. Urine was collected between 10 AM and 6 PM, as well as between 10 PM and 6 AM, and the amounts of urinary 6-hydroxy-melatonin sulfate (aMT6s) were determined by RIA. Compared to placebo, (R)-carvedilol increased heart rate during exercise (+4%, P < 0.05) and recovery (+10%, P < 0.05); (S)-carvedilol decreased heart rate during exercise (,14%, P < 0.05) and recovery (,6%, P < 0.05), and systolic blood pressure during exercise (,12%, P < 0.05); (R,S)-carvedilol decreased heart rate during exercise (,11%, P < 0.05), and systolic blood pressure at rest (,7%, P < 0.05) and during exercise (,10%, P < 0.05). None of the agents had any significant effect on the release of aMT6s. Our results indicate that only (S)-carvedilol causes beta-blockade, whereas (R)-carvedilol appears to increase sympathetic tone, presumably as a physiological reaction to the decrease of blood pressure caused by alpha-blockade. None of the drugs had any influence on melatonin release. The weak clinical net effect of beta-blockade of (R,S)-carvedilol at rest might be one reason why this drug causes fewer side effects than other beta-blockers, such as a reduction of nocturnal melatonin release. Chirality 13:342,346, 2001. © 2001 Wiley-Liss, Inc. [source] | |||||||||||||