title: Normalization of deranged signal transduction in lymphocytes of COPD patients by the novel calcium channel blocker H-DHPM.
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).
authors.affiliation: Department of Biochemistry, VP Chest Institute, University of Delhi, Delhi, India.
authors.forename: Sushma
authors.initials: S
authors.lastname: Manral
authors.forename: Sumati
authors.initials: S
authors.lastname: Bhatia
authors.forename: Rajesh
authors.initials: R
authors.lastname: Sinha
authors.forename: Ajit
authors.initials: A
authors.lastname: Kumar
authors.forename: Vishwajeet
authors.initials: V
authors.lastname: Rohil
authors.forename: Anu
authors.initials: A
authors.lastname: Arya
authors.forename: Ashish
authors.initials: A
authors.lastname: Dhawan
authors.forename: Pragya
authors.initials: P
authors.lastname: Arya
authors.forename: Rini
authors.initials: R
authors.lastname: Joshi
authors.forename: Sreerama C
authors.initials: SC
authors.lastname: Sreedhara
authors.forename: Sukanya
authors.initials: S
authors.lastname: Gangopadhyay
authors.forename: Surendra K
authors.initials: SK
authors.lastname: Bansal
authors.forename: Suvro
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Nabo K
authors.initials: NK
authors.lastname: Chaudhury
authors.forename: Vannan K
authors.initials: VK
authors.lastname: Vijayan
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
authors.forename: Virinder S
authors.initials: VS
authors.lastname: Parmar
authors.forename: Anthony L
authors.initials: AL
authors.lastname: DePass
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Prasad
authors.forename: Hanumantharao G
authors.initials: HG
authors.lastname: Raj
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011744:Pyrimidinones / Q000737:chemistry / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D012907:Smoking
chemical_list: D002121:Calcium Channel Blockers; D002614:Chelating Agents; D011744:Pyrimidinones; C561578:ethyl 4-(4'-heptanoyloxyphenyl)-6-methyl-3,4-dihydropyrimidin-2-one-5-carboxylate; D009569:Nitric Oxide; D004533:Egtazic Acid; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011493:Protein Kinase C; D002118:Calcium