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Phospholipase C activator m-3M3FBS affects Ca2+ homeostasis independently of phospholipase C activation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
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2004 (English)In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 143, no 1, 3-7 p.Article in journal (Refereed) Published
Abstract [en]

In this study, we have investigated responses to the phospholipase C (PLC) activator m-3M3FBS in SH-SY5Y human neuroblastoma cells. As measured using fura-2, m-3M3FBS caused a slowly developing - full response was obtained within 4-6 min - Ca(2+) elevation both in the presence and absence of extracellular Ca(2+), indicating Ca(2+) release from intracellular stores, putatively from endoplasmic reticulum and mitochondria. PLC activity was also measured using two methods, the classical ion-exchange separation and the more novel fluorescent real-time method. In the time frame in which m-3M3FBS caused Ca(2+) elevation (up to 7 min), no PLC activation was detected. Instead, more than 20 min were required to see any inositol phosphate generation in response to m-3M3FBS. m-3M3FBS also interfered with store-operated Ca(2+) influx and Ca(2+) extrusion. In conclusion, m-3M3FBS cannot be considered either potent or specific PLC activator.

Place, publisher, year, edition, pages
2004. Vol. 143, no 1, 3-7 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-91904DOI: 10.1038/sj.bjp.0705911PubMedID: 15302681OAI: oai:DiVA.org:uu-91904DiVA: diva2:164781
Available from: 2004-05-12 Created: 2004-05-12 Last updated: 2013-09-18Bibliographically approved
In thesis
1. Investigation on Pre- and Postsynaptic Ca2+ Signaling in Neuronal Model Systems
Open this publication in new window or tab >>Investigation on Pre- and Postsynaptic Ca2+ Signaling in Neuronal Model Systems
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Communication between neuronal and non-neuronal is called volume transmission when the released neurotransmitter (NT) acts via diffusion and affects several target cells. Both the neurosecretory and postsynaptic cell responses are linked to [Ca2+]i elevations.

In the present thesis the role of pre-and postsynaptic Ca2+ elevations has been investigated in the reconstituted "synapse" model comprised of NGF-differentiated PC12 and HEL cells as well as in SH-SY5Y neuroblastoma cells. In PC12 cells, both 70mM K+ and nicotine triggered NT release, which could be detected as a secondary [Ca2+]i increase in surrounding HEL cells. Both secretagogues shared the same voltage-dependent Ca2+ influx pathway as judged from the pharmacological profile blockers of voltage-gated Ca2+ channels. The coupling of electrical responses to the activation of Ca2+ signaling via muscarinic receptors in SH-SY5Y cells was also studied. These data revealed that depolarization caused a considerable potentiation of the muscarinic Ca2+ response. The potentiated Ca2+ increase was mainly dependent on the enhanced Ca2+ influx and to a lesser extent on [Ca2+]i release from intracellular stores. A phospholipase C (PLC) activator, m-3M3FBS was used to further study the role of G-protein coupled receptor (GPCR)-coupled Ca2+ signaling. However, it was found that m-3M3FBS instead triggered [Ca2+]i elevations independently of PLC activation.

In conclusion, the results indicate that the magnitude of NT release from PC12 cells is sufficient to cause a robust activation of neighboring target cells. Postsynaptic muscarinic signaling is amplified due to integration of electrical excitation and GPCR signaling. The PLC activator, m-3M3FBS is not suitable for studies of PLC-mediated signals in intact cells.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 52 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1361
Keyword
Physiology, calcium, neurotransmitter release, nicotine, depolarization, G-protein coupled receptor, muscarinic, phospholipase C, m-3M3FBS, Fysiologi
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-4300 (URN)91-554-5993-5 (ISBN)
Public defence
2004-06-05, Room B21, BMC, Husargatan 3, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-05-12 Created: 2004-05-12Bibliographically approved

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