The muscarinic effect of anhydroecgonine methyl ester, a crack cocaine pyrolysis product, impairs melatonin synthesis in the rat pineal gland

Pineal melatonin synthesis can be modulated by many peptides, including insulin. Because melatonin appears to alter leptin synthesis, in this work we aimed to investigate whether leptin would have a role on norepinephrine- (NE-)mediated melatonin synthesis in cultured rat pineal glands. According to our data, cultured rat pineal glands express leptin receptor isoform b (Ob-Rb). Pineal expression ofOb-RbmRNA was also observedin vivo. Administration of leptin (1 nM) associated with NE (1 µM) reduced melatonin content as well as arylalkylamine-N-acetyl transferase (AANAT) activity and expression in cultured pineal glands. Leptin treatment per se induced the expression of STAT3 in cultured pineal glands, but STAT3 does not participate in the leptin modulation of NE-mediated pineal melatonin synthesis. In addition, the expression of inducible cAMP early repressor (ICER) was further induced by leptin challenge when associated with NE. In conclusion, leptin inhibition of pineal melatonin synthesis appears to be mediated by a reduction in AANAT activity and expression as well as by increased expression ofIcermRNA. Peptidergic signaling within the pineal gland appears to be one of the most important signals which modulates melatonin synthesis; leptin, as a member of this system, is not an exception.

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Secretory Organelles of the Rat Pineal Gland: Electron Microscopic and Histochemical Studies in vivo and in vitro

Ciba Foundation Symposium - The Pineal Gland - Novartis Foundation Symposia ◽

10.1002/9780470715376.ch7 ◽

2008 ◽

pp. 147-175 ◽

Cited By ~ 1

Author(s):

Antti U. Arstila ◽

Hannu O. Kalimo ◽

Markku Hyyppa

Keyword(s):

Pineal Gland ◽

Electron Microscopic ◽

Rat Pineal Gland

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The effects of benzodiazepines on basal and isoproterenol-stimulated N-acetyltransferase activity by the rat pineal gland, in vivo and in vitro

Journal of Pineal Research ◽

10.1111/j.1600-079x.1991.tb00833.x ◽

1991 ◽

Vol 10 (3) ◽

pp. 151-158 ◽

Cited By ~ 5

Author(s):

W.D. Winters ◽

A. Yuwiler ◽

G.F. Oxenkrug

Keyword(s):

Pineal Gland ◽

Acetyltransferase Activity ◽

Rat Pineal Gland

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M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product

Scientific Reports ◽

10.1038/srep17555 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 6

Author(s):

Raphael Caio Tamborelli Garcia ◽

Livia Mendonça Munhoz Dati ◽

Larissa Helena Torres ◽

Mariana Aguilera Alencar da Silva ◽

Mariana Sayuri Berto Udo ◽

...

Keyword(s):

Methyl Ester ◽

Muscarinic Receptors ◽

Pyrolysis Product ◽

Anhydroecgonine Methyl Ester

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Synaptic ribbons of the rat pineal gland: responses to in-vivo and in-vitro treatment with inhibitors of protein synthesis

Cell and Tissue Research ◽

10.1007/bf00297490 ◽

1990 ◽

Vol 260 (1) ◽

pp. 63-67 ◽

Cited By ~ 11

Author(s):

J. A. Sousa Neto ◽

A. Seidel ◽

L. Vollrath ◽

B. Manz

Keyword(s):

Protein Synthesis ◽

Pineal Gland ◽

Synaptic Ribbons ◽

Rat Pineal Gland ◽

In Vitro Treatment

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Daily Rhythm in Pineal Phosphodiesterase (PDE) Activity Reflects Adrenergic/3′,5′-Cyclic Adenosine 5′-Monophosphate Induction of the PDE4B2 Variant

Endocrinology ◽

10.1210/en.2006-1420 ◽

2007 ◽

Vol 148 (4) ◽

pp. 1475-1485 ◽

Cited By ~ 24

Author(s):

Jong-So Kim ◽

Michael J. Bailey ◽

Anthony K. Ho ◽

Morten Møller ◽

Pascaline Gaildrat ◽

...

Keyword(s):

Pineal Gland ◽

Late Phase ◽

Daily Rhythm ◽

Camp Signaling ◽

Adrenergic Stimulation ◽

Melatonin Synthesis ◽

Dependent Protein ◽

Nocturnal Increase

The pineal gland is a photoneuroendocrine transducer that influences circadian and circannual dynamics of many physiological functions via the daily rhythm in melatonin production and release. Melatonin synthesis is stimulated at night by a photoneural system through which pineal adenylate cyclase is adrenergically activated, resulting in an elevation of cAMP. cAMP enhances melatonin synthesis through actions on several elements of the biosynthetic pathway. cAMP degradation also appears to increase at night due to an increase in phosphodiesterase (PDE) activity, which peaks in the middle of the night. Here, it was found that this nocturnal increase in PDE activity results from an increase in the abundance of PDE4B2 mRNA (∼5-fold; doubling time, ∼2 h). The resulting level is notably higher (>6-fold) than in all other tissues examined, none of which exhibit a robust daily rhythm. The increase in PDE4B2 mRNA is followed by increases in PDE4B2 protein and PDE4 enzyme activity. Results from in vivo and in vitro studies indicate that these changes are due to activation of adrenergic receptors and a cAMP-dependent protein kinase A mechanism. Inhibition of PDE4 activity during the late phase of adrenergic stimulation enhances cAMP and melatonin levels. The evidence that PDE4B2 plays a negative feedback role in adrenergic/cAMP signaling in the pineal gland provides the first proof that cAMP control of PDE4B2 is a physiologically relevant control mechanism in cAMP signaling.

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The Circadian Rhythms of STAT3 in the Rat Pineal Gland and Its Involvement in Arylalkylamine-N-Acetyltransferase Regulation

Life ◽

10.3390/life11101105 ◽

2021 ◽

Vol 11 (10) ◽

pp. 1105

Author(s):

Simona Moravcová ◽

Eva Filipovská ◽

Veronika Spišská ◽

Irena Svobodová ◽

Jiří Novotný ◽

...

Keyword(s):

Pineal Gland ◽

Enzyme Stability ◽

Suprachiasmatic Nuclei ◽

Stat3 Phosphorylation ◽

Activity Enhancement ◽

Transcription 3 ◽

Rat Pineal Gland ◽

Melatonin Production

In rodents, the melatonin production by the pineal gland is controlled through adrenergic signaling from the suprachiasmatic nuclei and regulation of the principal enzyme in its synthesis, arylalkylamine-N-acetyltransferase (AANAT). In the present study, we identified increased isoprenaline-induced aa-nat expression and nocturnal AANAT activity in the pineal glands in response to the silencing of the signal transducer and activator of transcription 3 (STAT3) with siRNA or STAT3 inhibitors WP1066 and AZD1480. This AANAT activity enhancement in vivo did not interfere with light-induced AANAT suppression. Systemic or in vitro lipopolysaccharide (LPS) administration markedly increased Stat3 expression and STAT3 phosphorylation, but it did not significantly affect AANAT expression or activity. Simultaneous LPS administration and Stat3 silencing enhanced the aa-nat transcription and AANAT activity to a similar extent as Stat3 inhibition without LPS co-administration. Furthermore, we describe the circadian rhythmicity in Stat3 expression and the phosphorylated form of STAT3 protein in the rat pineal gland. Our data suggest that the higher nocturnal endogenous level of STAT3 in the pineal gland decelerates or hampers the process of NA-induced AANAT activation or affects the AANAT enzyme stability.

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In Vitro and In Vivo Antioxidant Properties of Taraxacum officinale in Nω-Nitro-l-Arginine Methyl Ester (L-NAME)-Induced Hypertensive Rats

Antioxidants ◽

10.3390/antiox8080309 ◽

2019 ◽

Vol 8 (8) ◽

pp. 309

Author(s):

Olukayode O. Aremu ◽

Adebola O. Oyedeji ◽

Opeoluwa O. Oyedeji ◽

Benedicta N. Nkeh-Chungag ◽

Constance R. Sewani Rusike

Keyword(s):

Oxidative Stress ◽

Free Radical ◽

Methyl Ester ◽

Leaf Extract ◽

Radical Scavenging ◽

Free Radical Scavenging ◽

Hypertensive Rats ◽

Total Antioxidant

Oxidative stress has gained attention as one of the fundamental mechanisms responsible for the development of hypertension. The present study investigated in vitro and in vivo antioxidant effects of 70% ethanol-water (v/v) leaf and root extracts of T. officinale (TOL and TOR, respectively). Total phenolic and flavonoid content of plant extracts were assessed using Folin Ciocalteau and aluminium chloride colorimetric methods; while, 2,2-diphenyl-1-picrlhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) protocols were used to determine the free radical scavenging and total antioxidant capacities (TAC), respectively. The in vivo total antioxidant capacity and malondialdehyde acid (MDA) levels for lipid peroxidation tests were performed on organ homogenate samples from Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats treated with leaf extract, TOL (500 mg/kg/day) and TOR (500 mg/kg/day) for 21 days. Results showed that compared to TOR, TOL possessed significantly higher (p < 0.01) polyphenol (4.35 ± 0.15 compared to 1.14 ± 0.01) and flavonoid (23.17 ± 0.14 compared to 3 ± 0.05) content; free radical scavenging activity (EC50 0.37 compared to 1.34 mg/mL) and total antioxidant capacities (82.56% compared to 61.54% ABTS, and 156 ± 5.28 compared to 40 ± 0.31 FRAP) and both extracts showed no toxicity (LD50 > 5000 mg/kg). TOL and TOR significantly (p < 0.01) elevated TAC and reduced MDA levels in targets organs. In conclusion, T. officinale leaf extract possesses significant anti-oxidant effects which conferred significant in vivo antioxidant protection against free radical-mediated oxidative stress in L-NAME-induced hypertensive rats.

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