期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 613, 期 1-3, 页码 114-118出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2009.04.029
关键词
Diabetes; Capacitative calcium entry; Transient receptor potential canonical channel; Vasomotor function; Store-operated calcium channel
资金
- Heart and Stroke Foundation of British Columbia
- Heart and Stroke Foundation of Canada/AstraZeneca Canada Research Fellowship Award
Diabetes is associated with a perturbation of signaling pathways in vascular tissue, which causes vasomotor dysfunction such as hypertension. We have previously demonstrated that vessels from diabetic patients were more contractile than those from non-diabetic. However, in human vessels, the receptor-stimulated contraction is mainly due to enzymatic, rather than calcium signaling pathway. In this study, we hypothesized that the differential contractile response between diabetic and non-diabetic human vessels could be due to the receptor signaling to sarcoplasmic reticulum and the regulation of capacitative calcium entry. in saphenous vein samples (n = 20) collected from diabetic patients undergoing bypass surgery, the contraction initiated by the addition of the sarco-endoplasmatic reticulum calcium ATPase blocker, cyclopiazonic acid, was significantly higher than that in the vessels from non-diabetic patients (n = 26) (84.0 +/- 14.9% vs; 44.2 +/- 9.2%), and this contraction was inhibited by SKF-96365, an inhibitor of store-operated calcium channels. Pre-incubation with indomethacin reduced the cyclopiazonic acid-induced contraction in the non-diabetic veins, but had no effect on the diabetic ones. The gene expression of transient receptor potential canonical channels (TRPC)4 was upregulated by 22% in the diabetic vessels compared with the nondiabetic ones. However, the protein expression of TRPC1 and TRPC6 was downregulated in the diabetic group by 50%. We concluded that diabetes would modulate the capacitative calcium entry likely through the store-operated calcium channel specifically via the regulation of TRPC. (C) 2009 Elsevier B.V. All rights reserved.
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