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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 64 (1995), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Cyclic GMP accumulation in pinealocytes is elevated〉100-fold by norepinephrine (NE) through a mechanism involving conjoint activation of α1- and β1-adrenergic receptors. Little or no stimulation occurs if either α1- or β1-adrenergic receptors alone are activated. It appears that α1-adrenergic effects are mediated by Ca2+ acting in part through nitric oxide (NO), and β1-adrenergic effects are mediated by Gs. In the study presented here we investigated effects of adrenergic agonists or related postreceptor-active agents on stimulation of pineal cyclic GMP accumulation by the NO generator sodium nitroprusside (NP). The cyclic GMP response to NP (1 mM) was potentiated by NE and isoproterenol (ISO) but not by phenylephrine, indicating that activation of β1-adrenergic receptors potentiates the effects of NP. Similarly, vasoactive intestinal peptide (VIP), cholera toxin (CTX), and forskolin, all of which are known to mimic the effects of ISO in this system, also potentiated the effects of NP. In contrast, neither dibutyryl cyclic AMP nor agents that elevate intracellular Ca2+ levels caused marked potentiation of the effects of NP on pineal cyclic GMP. Depletion (90%) of Gsα by 21-h treatment with CTX reduced β-adrenergic potentiation of NP. These findings indicate that β-adrenergic agonists and VIP potentiate the effects of NP through a mechanism involving Gs. The molecular basis of this action may be an increase in guanylyl cyclase responsiveness to NO.
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 67 (1996), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Hydroxyindole-O-methyltransferase (HIOMT) plays an important role as the final enzyme in the synthesis of melatonin. Here we present the first evidence that retinoic acid (RA) stereoisomers are potent regulators of HIOMT in the human retinoblastoma-derived Y-79 cell line. Treatment with all-trans-, 13-cis-, and 9-cis-RA induced a gradual 10-fold increase in HIOMT activity and mRNA, without changing the levels of mRNA encoding glyceraldehyde-3-phosphate dehydrogenase, actin, S-antigen, and interphotoreceptor retinoid-binding protein. These findings point to the possibility that RA may play a physiological role in the regulation of human HIOMT.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: In this study the subunits of the dihydropyridine-sensitive L-type Ca2+ channels (L-channels) expressed in rat pinealocytes were characterized using reverse transcription (RT)-PCR analysis, and the modulation of these channels by adrenergic agonists and by pituitary adenylate cyclase-activating polypeptide (PACAP) was studied using the patch-clamp technique. RT-PCR analysis showed that rat pinealocytes expressed α1D, α2b, β2, and β4 Ca2+-channel subunit mRNAs. Other α1 subunit transcripts were either not expressed or present at very low levels, indicating that the pinealocytes express predominantly α1D L-channels. Electrophysiological studies confirmed that the pineal expressed a single population of L-channels. The L-channel currents were inhibited by two agonists that elevate cyclic AMP: the β-adrenergic agonist isoproterenol and PACAP. Similar inhibition was observed with a cyclic AMP analogue, 8-bromo-cyclic AMP. The presence of a cyclic AMP antagonist, Rp-adenosine 3′,5′-cyclic monophosphorothioate, blocked the inhibition by isoproterenol and PACAP. Norepinephrine, a mixed α- and β-adrenergic agonist, also inhibited the L-channel currents, but the inhibition was smaller. The smaller inhibition by norepinephrine was secondary to the simultaneous activation of α- and β-adrenergic receptors. These results indicate that (a) pinealocytes express predominantly α1D L-channels, and (b) the β-adrenergic agonist isoproterenol and PACAP inhibit the L-channel currents through elevation of cyclic AMP. However, an α-adrenergic-mediated mechanism also appears to be involved in the effect of norepinephrine on the L-channel currents.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd
    Journal of neurochemistry 74 (2000), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Melatonin production in the pineal gland is high at night and low during the day. This rhythm reflects circadian changes in the activity of serotonin N-acetyltransferase [arylalkylamine N-acetyltransferase (AA-NAT); EC 2.3.1.87], the penultimate enzyme in melatonin synthesis. The rhythm is generated by an endogenous circadian clock. In the chick, a clock is located in the pinealocyte, which also contains two phototransduction systems. One controls melatonin production by adjusting the clock and the other acts distal to the clock, via cyclic AMP mechanisms, to switch melatonin synthesis on and off. Unlike the clock in these cells, cyclic AMP does not appear to regulate activity by altering AA-NAT mRNA levels. The major changes in AA-NAT mRNA levels induced by the clock seemed likely (but not certain) to generate comparable changes in AA-NAT protein levels and AA-NAT activity. Cyclic AMP might also regulate AA-NAT activity via changes in protein levels, or it might act via other mechanisms, including posttranslational changes affecting activity. We measured AA-NAT protein levels and enzyme activity in cultured chick pineal cells and found that they correlated well under all conditions. They rose and fell spontaneously with a circadian rhythm. They also rose in response to agents that increase cyclic AMP. They were raised by agents that increase cyclic AMP, such as forskolin, and lowered by agents that decrease cyclic AMP, such as light and norepinephrine. Thus, both the clock and cyclic AMP can control AA-NAT activity by altering the total amount of AA-NAT protein. Effects of proteosomal proteolysis inhibitors suggest that changes in AA-NAT protein levels, in turn, reflect changes in the rate at which the protein is destroyed by proteosomal proteolysis. It is likely that cyclic AMP-induced changes in AA-NAT protein levels mediate rapid changes in chick pineal AA-NAT activity. Our results indicate that light can rapidly regulate the abundance of a specific protein (AA-NAT) within a photoreceptive cell.
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The circadian rhythms in melatonin production in the chicken pineal gland and retina reflect changes in the activity of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase; AA-NAT; EC 2.3.1.87). Here we determined that the chicken AA-NAT mRNA is detectable in follicular pineal cells and retinal photoreceptors and that it exhibits a circadian rhythm, with peak levels at night. AA-NAT mRNA was not detected in other tissues. The AA-NAT mRNA rhythm in the pineal gland and retina persists in constant darkness (DD) and constant lighting (LL). The amplitude of the pineal mRNA rhythm is not decreased in LL. Light appears to influence the phase of the clock driving the rhythm in pineal AA-NAT mRNA in two ways: The peak is delayed by ∼6 h in LL, and it is advanced by 〉4 h by a 6-h light pulse late in subjective night in DD. Nocturnal AA-NAT mRNA levels do not change during a 20-min exposure to light, whereas this treatment dramatically decreases AA-NAT activity. These observations suggest that the rhythmic changes in chicken pineal AA-NAT activity reflect, at least in part, clock-generated changes in mRNA levels. In contrast, changes in mRNA content are not involved in the rapid light-induced decrease in AA-NAT activity.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: NGFI-B (Nur77/Nr4a1) is a member of a nuclear steroid receptor subgroup that includes the related factors Nurr1 (Nr4a2) and NOR-1 (Nr4a3). These proteins do not have recognized ligands and in fact function independently as orphan receptors with transcriptional regulatory activity. In the present study, expression of the NGFI-B gene in the rat pineal gland was found to exhibit a robust circadian rhythm, with elevated levels of NGFI-B mRNA occurring at night. The rhythm of NGFI-B mRNA is translated into a circadian rhythm of NGFI-B protein, which accumulates in the nucleus of pinealocytes. In addition, there is a parallel marked nocturnal increase in pineal DNA binding activity to a NGFI-B response element (NBRE, AAAGGTCA). Pharmacological studies indicate that NGFI-B mRNA and protein levels are elevated via activation of adrenergic receptors. NGFI-B protein levels are also elevated by dibutyryl cyclic AMP, as in other systems. In the pineal gland, regulation of NGFI-B expression also involves the AP-1 protein Fra-2, based on studies with a transgenic Fra-2 knockdown rat, in which pineal NGFI-B expression increases. This set of observations extends the number of pineal genes that are known to be regulated by Fra-2, and also provides the first indication that a member of the NGFI-B group of nuclear receptors is involved in controlling gene expression in the pineal gland.
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  • 7
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The molecular core of the vertebrate circadian clock is a set of clock genes, whose products interact to control circadian changes in physiology. These clock genes are expressed in all tissues known to possess an endogenous self-sustaining clock, and many are also found in peripheral tissues. In the present study, the expression patterns of two clock genes, cBmal1 and cMOP4, were examined in the chicken, a useful model for analysis of the avian circadian system. In two tissues which contain endogenous clocks – the pineal gland and retina – circadian fluctuations of both cBmal1 and cMOP4 mRNAs were observed to be synchronous; highest levels occurred at Zeitgeber time 12. Expression of these genes is also rhythmic in several peripheral tissues; however, the phases of these rhythms differ from those in the pineal gland and retina: in the liver the peaks of cMOP4 and cBmal1 mRNAs are delayed 4–8 h and in the heart they are advanced by 4 h, relative to those in the pineal gland and retina. These results provide the first temporal characterization of cBmal1 and cMOP4 mRNAs in avian tissues: their presence in avian peripheral tissues indicates they may influence temporal features of daily rhythms in biochemical, physiological, and behavioral functions at these sites.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    [s.l.] : Macmillan Magazines Ltd.
    Nature 389 (1997), S. 699-701 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The techniques of colloidal chemistry permit the routine creation of semiconductor nanocrystals, whose dimensions are much smaller than those that can be realized using lithographic techniques. The sizes of such nanocrystals can be varied systematically to study quantum size effects or to make ...
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