Cholinergic signal transduction cascades in rat pinealocytes: functional and ontogenetic aspects

Schomerus, Christof; Korf, Horst‐Werner

doi:10.1051/rnd:19990303

Cited by 4 publications

(4 citation statements)

References 28 publications

(31 reference statements)

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“…The nature and function of cholinergic inputs still remain to be clarified. Their suggested roles are indicated in this diagram (18,43,56,58). ACh from cholinergic terminals increases intracellular Ca 2ϩ through nAChR and voltagegated Ca 2ϩ channel (VGCC).…”

Section: Discussionmentioning

confidence: 99%

“…The paracrine secreted glutamate is postulated to decrease cAMP via inhibitory G icoupled type-3 metabotropic glutamate receptors on nearby pinealocytes and to suppress NE-induced melatonin biosynthesis (for review, see Ref. 43). In addition, acetylcholine acting on muscarinic receptors also inhibits melatonin synthesis both through presynaptic inhibition of NE release from sympathetic terminals and by inhibiting the enzyme arylalkylamine Nacetyltransferase in rat pinealocytes (10,34).…”

Section: Discussionmentioning

confidence: 99%

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Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes

Yoon

Jung

Hille

et al. 2014

American Journal of Physiology-Cell Physiology

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Melatonin secretion from the pineal gland is triggered by norepinephrine released from sympathetic terminals at night. In contrast, cholinergic and parasympathetic inputs, by activating nicotinic cholinergic receptors (nAChR), have been suggested to counterbalance the noradrenergic input. Here we investigated whether adrenergic signaling regulates nAChR channels in rat pinealocytes. Acetylcholine or the selective nicotinic receptor agonist 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) activated large nAChR currents in whole cell patch-clamp experiments. Norepinephrine (NE) reduced the nAChR currents, an effect partially mimicked by a β-adrenergic receptor agonist, isoproterenol, and blocked by a β-adrenergic receptor antagonist, propranolol. Increasing intracellular cAMP levels using membrane-permeable 8-bromoadenosine (8-Br)-cAMP or 5,6-dichlorobenzimidazole riboside-3',5'-cyclic monophosphorothioate (cBIMPS) also reduced nAChR activity, mimicking the effects of NE and isoproterenol. Further, removal of ATP from the intracellular pipette solution blocked the reduction of nAChR currents, suggesting involvement of protein kinases. Indeed protein kinase A inhibitors, H-89 and Rp-cAMPS, blocked the modulation of nAChR by adrenergic stimulation. After the downmodulation by NE, nAChR channels mediated a smaller Ca(2+) influx and less membrane depolarization from the resting potential. Together these results suggest that NE released from sympathetic terminals at night attenuates nicotinic cholinergic signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes

Yoon

Jung

Hille

et al. 2014

American Journal of Physiology-Cell Physiology

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“…Acetylcholine receptor expression is consistent with anatomical evidence (5) that reveals the presence of nonsympathetic, probably parasympathetic, nerve fibers in the pineal gland of the rat and with biochemical studies that have shown the presence of both muscarinic (107) and nicotinic (108) cholinergic receptors. Furthermore, it has been shown that a cholinergic input to the rat pineal gland causes the release of glutamate, which has been reported to act via glutamate receptors on the pinealocyte membrane to inhibit melatonin synthesis (109,110).…”

Section: Nonspecialized Functional Gene Groupsmentioning

confidence: 99%

Night/Day Changes in Pineal Expression of >600 Genes

Bailey

Coon

Carter

et al. 2009

Journal of Biological Chemistry

136

211

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The pineal gland plays an essential role in vertebrate chronobiology by converting time into a hormonal signal, melatonin, which is always elevated at night. Here we have analyzed the rodent pineal transcriptome using Affymetrix GeneChip technology to obtain a more complete description of pineal cell biology. The effort revealed that 604 genes (1,268 probe sets) with Entrez Gene identifiers are differentially expressed greater than 2-fold between midnight and mid-day (false discovery rate <0.20). Expression is greater at night in ϳ70%. These findings were supported by the results of radiochemical in situ hybridization histology and quantitative real time-PCR studies. We also found that the regulatory mechanism controlling the night/ day changes in the expression of most genes involves norepinephrine-cyclic AMP signaling. Comparison of the pineal gene expression profile with that in other tissues identified 334 genes (496 probe sets) that are expressed greater than 8-fold higher in the pineal gland relative to other tissues. Of these genes, 17% are expressed at similar levels in the retina, consistent with a common evolutionary origin of these tissues. Functional categorization of the highly expressed and/or night/day differentially expressed genes identified clusters that are markers of specialized functions, including the immune/inflammation response, melatonin synthesis, photodetection, thyroid hormone signaling, and diverse aspects of cellular signaling and cell biology. These studies produce a paradigm shift in our understanding of the 24-h dynamics of the pineal gland from one focused on melatonin synthesis to one including many cellular processes.A defining feature of the pineal gland is a 24-h rhythm in melatonin synthesis. Melatonin provides vertebrates with a circulating signal of time and is essential for optimal integration of physiological functions with environmental lighting on a daily and seasonal basis (1-4).The melatonin rhythm in mammals is driven by a circadian clock located in the suprachiasmatic nucleus (SCN), 13 which is hard-wired to the pineal gland by a polysynaptic pathway that courses through central and peripheral neuronal structures. The pineal gland is innervated by projections from the superior cervical ganglia (SCG) in the form of a dense network of catecholamine-containing sympathetic fibers. Activation of the SCN 3 pineal pathway occurs at night and results in the release

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“…On the other hand, the role of parasympathetic innervation is still not clear. In rats, the muscarinic receptors are present only in the developmental phase [23]. In adult rats, the only cholinergic receptors detected are nicotinic, which leads to a great entrance of calcium ions and the release of glutamate.…”

Section: Melatoninergic Systemmentioning

confidence: 99%

Melatoninergic System in Parkinson’s Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms

Mack

Schamne

Sampaio

et al. 2016

Oxidative Medicine and Cellular Longevity

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Melatonin is synthesized by several tissues besides the pineal gland, and beyond its regulatory effects in light-dark cycle, melatonin is a hormone with neuroprotective, anti-inflammatory, and antioxidant properties. Melatonin acts as a free-radical scavenger, reducing reactive species and improving mitochondrial homeostasis. Melatonin also regulates the expression of neurotrophins that are involved in the survival of dopaminergic neurons and reduces α-synuclein aggregation, thus protecting the dopaminergic system against damage. The unbalance of pineal melatonin synthesis can predispose the organism to inflammatory and neurodegenerative diseases such as Parkinson's disease (PD). The aim of this review is to summarize the knowledge about the potential role of the melatoninergic system in the pathogenesis and treatment of PD. The literature reviewed here indicates that PD is associated with impaired brain expression of melatonin and its receptors MT1 and MT2. Exogenous melatonin treatment presented an outstanding neuroprotective effect in animal models of PD induced by different toxins, such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, paraquat, and maneb. Despite the neuroprotective effects and the improvement of motor impairments, melatonin also presents the potential to improve nonmotor symptoms commonly experienced by PD patients such as sleep and anxiety disorders, depression, and memory dysfunction.

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Cholinergic signal transduction cascades in rat pinealocytes: functional and ontogenetic aspects

Cited by 4 publications

References 28 publications

Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes

Modulation of nicotinic receptor channels by adrenergic stimulation in rat pinealocytes

Night/Day Changes in Pineal Expression of >600 Genes

Melatoninergic System in Parkinson’s Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms

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