title: Human epidermoid A431 cells express functional nicotinic acid receptor HM74a.
abstract: Nicotinic acid (niacin) has been used clinically to manage dyslipidemia for many years. The molecular target of nicotinic acid was unknown until the recent revelation of human G-coupled receptor HM74a as the high affinity receptor for nicotinic acid. In searching for a cell line expressing endogenous human HM74a receptor, we have identified that the A431 cell line, a human epidermoid cell line, expresses a high level of HM74a receptor. An HM74a-specific real time PCR probe set was designed and the mRNA levels of HM74a in A431 and 32 other cultured cell lines were measured quantitatively. When the mRNA expression of HM74a in A431 cells was compared to that in human primary preadipocytes, adipocytes and adipose tissue, we found that the level in A431 was about 10- fold higher than that in adipocytes and adipose tissue. The ratio of HM74a:HM74 mRNA was measured quantitatively and it was determined to be 3:2 in A431 cells. The function of the HM74a receptor in A431 cells was evaluated for its ability to inhibit forskolin-induced cAMP production. Pertussis toxin treatment abolished the inhibition. Our data suggest that the A431 cell line may serve as a cellular model for further investigation of niacin/HM74a-mediated signal transduction in modulating metabolism. A431 cell line may also provide a valuable cell model to study prostaglandin production upon HM74a activation to improve our understanding of niacin/HM74a-mediated skin flushing.
authors.affiliation: Endocrine Therapeutics and Metabolic Disorders Team, Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, LLC, 1000 Route 202, Raritan, NJ 08869, USA. lzhou172@yahoo.com
authors.forename: Lubing
authors.initials: L
authors.lastname: Zhou
authors.forename: Yuting
authors.initials: Y
authors.lastname: Tang
authors.forename: Ellen V
authors.initials: EV
authors.lastname: Cryan
authors.forename: Keith T
authors.initials: KT
authors.lastname: Demarest
mesh_terms: D000595:Amino Acid Sequence; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000032:analysis; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism*
chemical_list: C530636:HCAR2 protein, human; C473653:HCAR3 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D011978:Receptors, Nicotinic; D000242:Cyclic AMP