Synthesis, storage and release of acetylcholine by a noradrenergic pheochromocytoma cell line

Greene, Lloyd A.; Rein, Glen

doi:10.1038/268349a0

Cited by 248 publications

(112 citation statements)

References 18 publications

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“…In a mouse mutant containing reduced acetylcholinesterase activity, which increased levels of ambient acetylcholine, muscarinic receptors were expressed in the cytoplasm instead of on the plasma membrane (Bernard et al, 2003). NGFdifferentiated PC12 cells synthesize and release acetylcholine (Greene and Rein, 1977), which could lead to elevated levels of acetylcholine. In response to sustained agonist stimulation, m 2 and m 4 muscarinic receptors undergo desensitization, which involves dynamin-dependent pathways and either clathrin-independent or clathrin-dependent processes, respectively (Volpicelli et al, 2001;Delaney et al, 2002).…”

Section: Implications Of Sequestered Gpcr/kir3 Channel Signaling Compmentioning

confidence: 99%

“…Recently, Bernard et al (2003) found that muscarinic receptors were predominantly localized to the cytoplasm in neurons of a mouse mutant that contained elevated levels of acetylcholine. NGF-differentiated PC12 cells can synthesize and release acetylcholine (Greene and Rein, 1977), which could lead to elevated levels of acetylcholine. Bernard et al (2003) found that exposing the neurons to a nonselective muscarinic receptor antagonist (atropine) prevented the translocation of endogenous muscarinic receptors from the cell surface to the cytoplasm.…”

Section: Absence Of Muscarinic Receptoractivated Kir32 Currents In Nmentioning

confidence: 99%

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Coregulation of Natively Expressed Pertussis Toxin-Sensitive Muscarinic Receptors with G-Protein-Activated Potassium Channels

Clancy¹,

Boyer²,

Slesinger³

2007

Journal of Neuroscience

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Section: Implications Of Sequestered Gpcr/kir3 Channel Signaling Compmentioning

confidence: 99%

Section: Absence Of Muscarinic Receptoractivated Kir32 Currents In Nmentioning

confidence: 99%

Coregulation of Natively Expressed Pertussis Toxin-Sensitive Muscarinic Receptors with G-Protein-Activated Potassium Channels

Clancy¹,

Boyer²,

Slesinger³

2007

Journal of Neuroscience

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“…At baseline, cell surface m4 could be activated by ACh released by PC12 cells (26,27) and hence internalized. Substantial levels of choline acetyltransferase activity have been measured and therefore the PC12 cells used in this study synthesize ACh.…”

Section: Rab5-dependent Trafficking Of M4mentioning

confidence: 99%

Rab5-dependent Trafficking of the m4 Muscarinic Acetylcholine Receptor to the Plasma Membrane, Early Endosomes, and Multivesicular Bodies

Volpicelli

Lah

Levey

2001

Journal of Biological Chemistry

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The m4 subtype of muscarinic acetylcholine receptor regulates many physiological processes and is a novel therapeutic target for neurologic and psychiatric disorders. However, little is known about m4 regulation because of the lack of pharmacologically selective ligands. A crucial component of G protein-coupled receptor regulation is intracellular trafficking. We thus used subtype-specific antibodies and quantitative immunocytochemistry to characterize the intracellular trafficking of m4. We show that following carbachol stimulation, m4 co-localizes with transferrin, and the selective marker of early endosomes, EEA1. In addition, m4 intracellular localization depends on Rab5 activity. The dominant negative Rab5S34N inhibits m4 endocytosis initially following carbachol stimulation, and reduces the size of m4 containing vesicles. The constitutively active Rab5Q79L enhances m4 intracellular distribution, even in unstimulated cells. Rab5Q79L also produces strikingly enlarged vacuoles, which by electron microscopy contain internal vesicles, suggesting that they are multivesicular bodies. m4 localizes both to the perimeter and interior of these vacuoles. In contrast, transferrin localizes only to the vacuole perimeter, demonstrating divergence of m4 trafficking from the pathway followed by constitutively endocytosed transferrin. We thus suggest a novel model by which multivesicular bodies sort G protein-coupled receptors from a transferrin-positive recycling pathway to a nonrecycling, possibly degradative pathway.

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“…PC12 cells take up choline and rapidly convert the accumulated choline to ACh (Greene & Rein, 1977c;Melega & Howard, 1981). ACh is compartmentalized into specific storage granules and thereby protected from degradation by the normally high levels of AChE activity in these cells (Rebois et al, 1980;Melega & Howard, 1981).…”

Section: Alterations In Choline and Ach Levels In Scrapie-infected Pcmentioning

confidence: 99%

Alterations in neurotransmitter-related enzyme activity in scrapie-infected PC12 cells

Rubenstein

Deng

Scalici

et al. 1991

Journal of General Virology

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Enzyme activities associated with the neurotransmitter pathways in nerve growth factor-treated, 139A scrapie strain-infected PCI2 cells were examined. Since these cells show no morphological alterations during the time of agent replication, any scrapie-induced effects would have to be associated with non-vital cellular functions. When compared to controls, infection with the 139A scrapie strain resulted in decreased activity of the cholinergic pathway-related enzymes, choline acetyltransferase and acetylcholinesterase. However, the adrenergic pathway was unaffected by scrapie infection as evidenced by unaltered tyrosine hydroxylase activity, the putative rate-limiting enzyme in the synthesis of catecholamines. The effects of the 139A scrapie strain on the cholinergic system appeared to be dose-dependent and were first detected prior to the detection of scrapie agent replication in these cells. Furthermore, the altered enzymic activities observed were not the result of contaminating material in the scrapie brain homogenate because similar results were obtained when partially purified scrapie preparations were used as the inoculum. These scrapie agentinduced alterations in specific neuronal properties suggest a mechanism for the clinical manifestations observed in scrapie and perhaps other related central nervous system disorders.

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Synthesis, storage and release of acetylcholine by a noradrenergic pheochromocytoma cell line

Cited by 248 publications

References 18 publications

Coregulation of Natively Expressed Pertussis Toxin-Sensitive Muscarinic Receptors with G-Protein-Activated Potassium Channels

Coregulation of Natively Expressed Pertussis Toxin-Sensitive Muscarinic Receptors with G-Protein-Activated Potassium Channels

Rab5-dependent Trafficking of the m4 Muscarinic Acetylcholine Receptor to the Plasma Membrane, Early Endosomes, and Multivesicular Bodies

Alterations in neurotransmitter-related enzyme activity in scrapie-infected PC12 cells

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