We have studied the ability of cGMP and cAMP to modulate platelet-derived growth factor (PDGF)-stimulated 2-deoxy-d-glucose (deGlc) transport in primary cultures of vascular smooth muscle cells (VMSC) from rat aorta. PDGF stimulated deGlc transport in a time- and concentration-dependent manner. 8-Bromo-cGMP and atrial natriuretic peptide(1–28) [ANP(1–28)] were found to reduce PDGF-stimulated deGlc transport without affecting basal (unstimulated) transport activity. In contrast, 8-bromo-cAMP and dibutyryl-cAMP stimulated basal deGlc transport 2-fold and were without effect on PDGF-stimulated deGlc transport. 8-Bromo-cGMP also inhibited 8-bromo-cAMP-stimulated deGlc transport. The stimulation of deGlc transport by PDGF was sensitive to the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase (MEK) inhibitor PD98059, and we show that ERK1/2 was activated by PDGF. Neither 8-bromo-cGMP nor ANP(1–28) inhibited PDGF-stimulated ERK activation, suggesting that the effects of cGMP and ANP(1–28) were not mediated by inhibition of this kinase. Our data also argue against a role for cGMP-dependent protein kinase in mediating the effects of cGMP or ANP(1–28). Collectively, our data suggest that in VSMC: (i) cGMP and cAMP have opposing effects on deGlc transport; (ii) PDGF and cAMP have common elements in the pathways by which they activate deGlc transport; and (iii) a common element may be the target of the cGMP-mediated inhibition of deGlc transport.
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February 2001
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Research Article|
January 25 2001
Regulation of glucose transport in aortic smooth muscle cells by cAMP and cGMP
Christopher J. MacKENZIE;
Christopher J. MacKENZIE
1
*Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
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Jill M. WAKEFIELD;
Jill M. WAKEFIELD
*Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
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Fiona CAIRNS;
Fiona CAIRNS
*Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
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Anna F. DOMINICZAK;
Anna F. DOMINICZAK
†Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow G11 6NT, Scotland, U.K.
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Gwyn W. GOULD
Gwyn W. GOULD
2
*Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, Davidson Building, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
2To whom correspondence should be addressed (e-mail G.Gould@bio.gla.ac.uk).
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Publisher: Portland Press Ltd
Received:
August 29 2000
Revision Received:
October 24 2000
Accepted:
November 02 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2001
2001
Biochem J (2001) 353 (3): 513–519.
Article history
Received:
August 29 2000
Revision Received:
October 24 2000
Accepted:
November 02 2000
Citation
Christopher J. MacKENZIE, Jill M. WAKEFIELD, Fiona CAIRNS, Anna F. DOMINICZAK, Gwyn W. GOULD; Regulation of glucose transport in aortic smooth muscle cells by cAMP and cGMP. Biochem J 1 February 2001; 353 (3): 513–519. doi: https://doi.org/10.1042/bj3530513
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