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Biochimie. 2011 Jul;93(7):1146-56. doi: 10.1016/j.biochi.2011.04.004. Epub 2011 Apr 20.

Normalization of deranged signal transduction in lymphocytes of COPD patients by the novel calcium channel blocker H-DHPM.

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1
Department of Biochemistry, VP Chest Institute, University of Delhi, Delhi, India.

Abstract

Investigations on the role of intracellular Ca(2+) ion concentration in the mechanism of development of COPD in smokers and non-smokers were carried out. The intracellular Ca(2+) levels were found to be increased in human lymphocytes in patients with COPD as compared to non-smokers and smokers without COPD. The investigations reveal an association in altered intracellular Ca(2+) regulation in lymphocytes and severity of COPD, by means of significant activation of Protein kinase C and inducible nitric oxide synthase (iNOS). The effect of a novel calcium channel blocker ethyl 4-(4'-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate (H-DHPM) as a potential candidate for the treatment of COPD was also investigated. H-DHPM treated cells showed a decrease in intracellular Ca(2+) level as compared to the control cells. Molecular studies were carried out to evaluate the expression profile of NOS isoforms in human lymphocytes and it was shown that H-DHPM decreases the increased iNOS in COPD along with reestablishing the normal levels of endothelial nitric oxide synthase (eNOS). The results of H-DHPM were comparable with those of Amlodipine, a known calcium channel blocker. Calcium channel blocker H-DHPM proves to be a potential candidate for the treatment of COPD and further clinical studies are required to prove its role in the treatment of pulmonary hypertension (PH).

PMID:
21527308
DOI:
10.1016/j.biochi.2011.04.004
[Indexed for MEDLINE]
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