Metabolic effects of newly synthesized phosphodiesterase-3 inhibitor 6-4-(4-methylpiperidin-1-yl)-4-oxobutoxy-4-methylquinolin-2(1H)-one on rat adipocytes

Alinejad, B. and Shafiee-Nick, R. and Sadeghian, H. and Ghorbani, A. (2015) Metabolic effects of newly synthesized phosphodiesterase-3 inhibitor 6-4-(4-methylpiperidin-1-yl)-4-oxobutoxy-4-methylquinolin-2(1H)-one on rat adipocytes. DARU, Journal of Pharmaceutical Sciences, 23 (1).

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Abstract

Background: Clinical use of selective PDE3 inhibitors as cardiotonic agents is limited because of their chronotropic and lipolytic side effects. In our previous work, we synthesized a new PDE3 inhibitor named MC2 (6-4-(4-methylpiperidin-1-yl)-4-oxobutoxy-4-methylquinolin-2(1H)-one) which produced a high positive inotropic action with a negative chronotropic effect. This work was done to evaluate the effects of MC2 on adipocytes and compare its effects with those of amrinone and cilostamide. Methods: Preadipocytes were isolated from rat adipose tissue and differentiated to adipocyte in the presence of cilostamide, amrinone or MC2. Lipolysis and adipogenesis was evaluated by measuring glycerol level and Oil Red O staining, respectively. Adipocyte proliferation and apoptosis were determined with MTT assay and Annexin V/PI staining, respectively. Results: Differentiation to adipocyte was induced by amrinone but not by cilostamide or MC2. Basal and isoproterenol-stimulated lipolysis significantly increased by cilostamide (p < 0.05). Similarly, amrinone enhanced the stimulated lipolysis (p < 0.01). On the other hand, MC2 significantly decreased both adipogenesis (p < 0.05) and stimulated lipolysis (p < 0.001). Also, incubation of differentiated adipocytes with MC2 caused the loss of cell viability, which was associated with the elevation in apoptotic rate (p < 0.05). Conclusion: Our data indicate that selective PDE3 inhibitors produce differential effects on adipogenesis and lipolysis. MC2 has proapoptotic and antilipolytic effects on adipocytes and does not stimulate adipogenesis. Therefore, in comparison with the clinically available selective PDE3 inhibitors, MC2 has lowest metabolic side effects and might be a good candidate for treatment of congestive heart failure. © 2015 Alinejad et al.; licensee BioMed Central.

Item Type: Article
Additional Information: Cited By :5 Export Date: 16 February 2020 CODEN: DJTSF Correspondence Address: Shafiee-Nick, R.; Department of Pharmacology, School of Medicine, Mashhad University of Medical SciencesIran
Uncontrolled Keywords: Adipogenesis Amrinone Cilostamide Lipolysis Phosphodiesterases 6 4 (4 methylpiperidin 1 yl) 4 oxobutoxy 4 methylquinolin 2 (1h) one glycerol isoprenaline lipocortin 5 phosphodiesterase III inhibitor unclassified drug 6-(4-(4-methylpiperidin-1-yl)-4-oxobutoxy)-4-methylquinolin-2(1H)-one piperidine derivative quinolone derivative adipocyte adipose tissue animal cell animal experiment animal tissue apoptosis Article cell differentiation cell isolation cell proliferation cell stimulation cell viability controlled study drug synthesis incubation time male MTT assay nonhuman rat staining animal cell culture cell survival drug effects physiology synthesis Wistar rat Adipocytes Animals Cells, Cultured Phosphodiesterase 3 Inhibitors Piperidines Quinolones Rats Rats, Wistar
Subjects: QV pharmacology
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib5 lib5
Date Deposited: 11 May 2020 19:23
Last Modified: 11 May 2020 19:23
URI: http://eprints.mums.ac.ir/id/eprint/18745

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