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Direct involvement of G protein alpha(q/11) subunit in regulation of muscarinic receptor-mediated sAPP alpha release

Title
Direct involvement of G protein alpha(q/11) subunit in regulation of muscarinic receptor-mediated sAPP alpha release
Authors
Kim, JHKim, HJ
Ewha Authors
김화정
SCOPUS Author ID
김화정scopus
Issue Date
2005
Journal Title
ARCHIVES OF PHARMACAL RESEARCH
ISSN
0253-6269JCR Link
Citation
vol. 28, no. 11, pp. 1275 - 1281
Keywords
sAPP alpha releasemuscarinic receptorG proteinepidermal growth factor receptorSH-SY5Y cells
Publisher
PHARMACEUTICAL SOCIETY KOREA
Indexed
SCIE; SCOPUS; KCI WOS scopus
Abstract
The G(q/11) protein-coupled receptors, such as muscarinic (M1 & M3) receptors, have been shown to regulate the release of a soluble amyloid precursor protein (sAPP alpha) produced from a-secretase processing. However, there is no direct evidence for the precise characteristics of G proteins, and the signaling mechanism for the regulation of G(q/11) protein-coupled receptor-mediated sAPP alpha release is not clearly understood. This study examined whether the muscarinic receptor-mediated release of sAPP alpha is directly regulated by G alpha(q/11) proteins. The HEK293 cells were transiently cotransfected with muscarinic M3 receptors and a dominant-negative minigene construct of the G protein alpha subunit. The sAPP alpha release in the media was measured using an antibody specific for sAPP. The sAPP alpha release enhancement induced by muscarinic receptor stimulation was decreased by a G(q/11) minigene construct, whereas it was not blocked by a control minigene construct (the G alpha carboxy peptide in random order, G alpha(q)R) or G alpha constructs. This indicated a direct role of the G alpha(q/11) protein in the regulation of muscarinic M3 receptor-mediated sAPP alpha release. We also investigated whether the transactivation of the epidermal growth factor receptor (EGFR) by a muscarinic agonist could regulate the sAPP alpha release in SH-SY5Y cells. Pretreatment of a specific EGFR kinase inhibitor, tyrophostin AG1478 (250 nM), blocked the EGIF-stimulated sAPP alpha release, but did not block the oxoM-stimulated sAPP alpha release. This demonstrated that the transactivation of the EGFR by muscarinic receptor activation was not involved in the muscarinic receptor-mediated sAPP alpha release.
DOI
10.1007/BF02978212
Appears in Collections:
약학대학 > 약학과 > Journal papers
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