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Similarly Potent Inhibition of Adenylyl Cyclase by P-Site Inhibitors in Hearts from Wild Type and AC5 Knockout Mice

Title
Similarly Potent Inhibition of Adenylyl Cyclase by P-Site Inhibitors in Hearts from Wild Type and AC5 Knockout Mice
Authors
Braeunig J.H.Schweda F.Han P.-L.Seifert R.
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2013
Journal Title
PLoS ONE
ISSN
1932-6203JCR Link
Citation
vol. 8, no. 7
Indexed
SCIE; SCOPUS WOS scopus
Abstract
Adenylyl cyclase type 5 (AC5) was described as major cardiac AC isoform. The knockout of AC5 (AC5KO) exerted cardioprotective effects in heart failure. Our study explored the impact of AC5KO on mouse heart AC activities and evaluated putative AC5-selective inhibitors. In cardiac membranes from AC5KO mice, basal AC activity was decreased, while AC stimulation was intact. The putative AC5-selective P-site inhibitors SQ22,536 [9-(tetra-hydro-2-furanyl)-9H-purin-6-amine], vidarabine (9-β-D-arabinosyladenine) and NKY80 [2-amino-7-(2-furanyl)-7,8-dihydro-5(6H)-quinazolinone] inhibited recombinant AC5 more potently than AC2 and AC1, but selectivity was only modest (∼4-40-fold). These compounds inhibited cardiac AC from WT and AC5KO mice with similar potencies. In conclusion, AC regulation in AC5KO hearts was unimpaired, questioning the supposed dominant role of AC5 in the heart. Moreover, the AC inhibitors SQ22,536, NKY80 and vidarabine lack adequate selectivity for AC5 and, therefore, do not present suitable tools to study AC5-specific functions. © 2013 Braeunig et al.
DOI
10.1371/journal.pone.0068009
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일반대학원 > 뇌·인지과학과 > Journal papers
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