title: Involvement of anandamide transporter in calcitonin gene-related peptide expression stimulated by nitroglycerin and influence of ALDH2 Glu504Lys polymorphism.
abstract: 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.
authors.affiliation: *Department of Cardiology, Xiangya Hospital, Central South University, Changsha, China; †Institute of Clinical Pharmacology, Central South University, Changsha, China; and ‡Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha, China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Peng
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Rui-Zheng
authors.initials: RZ
authors.lastname: Shi
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Li
authors.forename: Tian-Lun
authors.initials: TL
authors.lastname: Yang
mesh_terms: D000328:Adult; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology; D044466:Asian People / Q000235:genetics; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics*; D063388:Endocannabinoids / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D026901:Membrane Transport Proteins / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D011110:Polymorphism, Genetic; D053284:Polyunsaturated Alkamides / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D026901:Membrane Transport Proteins; D053284:Polyunsaturated Alkamides; D012333:RNA, Messenger; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D005996:Nitroglycerin; D015740:Calcitonin Gene-Related Peptide; C078814:anandamide; C107594:N-(4-hydroxyphenyl)arachidonylamide