Involvement of anandamide transporter in calcitonin gene-related peptide expression stimulated by nitroglycerin and influence of ALDH2 Glu504Lys polymorphism
| Autor: | Xiao-Ping Chen, Yuan-Jian Li, Tian-Lun Yang, Li-Ming Peng, Lei Chen, Ruizheng Shi |
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| Rok vydání: | 2014 |
| Předmět: |
Adult
Male medicine.medical_specialty Genotype Polyunsaturated Alkamides Calcitonin Gene-Related Peptide Arachidonic Acids Calcitonin gene-related peptide Peripheral blood mononuclear cell chemistry.chemical_compound Nitroglycerin Asian People Internal medicine medicine Humans RNA Messenger ALDH2 Pharmacology Messenger RNA Polymorphism Genetic Aldehyde Dehydrogenase Mitochondrial Membrane Transport Proteins Transporter Anandamide Aldehyde Dehydrogenase Endocrinology chemistry Gene Expression Regulation Calcitonin AM404 cardiovascular system Leukocytes Mononuclear lipids (amino acids peptides and proteins) Cardiology and Cardiovascular Medicine circulatory and respiratory physiology Endocannabinoids |
| Zdroj: | Journal of cardiovascular pharmacology. 64(5) |
| ISSN: | 1533-4023 |
| Popis: | The aim of this study was to investigate whether N-arachidonic acid ethanolamine (anandamide, AEA) transporter contributed to calcitonin gene-related peptide (CGRP) expression mediated by nitroglycerin (GTN) in peripheral blood mononuclear cells (PBMCs) of healthy volunteers and its association with the mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism. In 10 ALDH2*2-genotyped Chinese volunteers, we assessed the activity of AEA transporter and expression of CGRP messenger ribonucleic acid (mRNA) in cultured PBMCs treated with different concentration of GTN with or without pretreatment with AM404 (the AEA transporter blocker). In this study, the activity of AEA transporter and expression of CGRP mRNA elevated with the increase in the concentration of GTN. Pretreatment of the cells with AM404 (1 μM) 2 hours before GTN reduced the GTN-induced increase in both AEA transporter activity and CGRP mRNA expression significantly, and cells with the ALDH2*1/*1 homozygote genotype showed significantly higher activity of AEA transporter and CGRP mRNA expression than carriers of the ALDH2*2 allele. Therefore, we strongly suggested that GTN can stimulate CGRP expression by elevating the AEA transporter activity, which is affected by ALDH2 Glu504Lys polymorphism. |
| Databáze: | OpenAIRE |
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