title: Inhibitory effect of β-hydroxybutyric acid on L-type Ca(2+) current under β-adrenergic stimulation in guinea pig cardiac ventricular myocytes.
abstract: Severe ketoacidosis induces heart failure and cardiac arrest, but its mechanism is unknown. Recently, hydroxy-carboxylic acid receptor 2 (HCA(2)) was found to be a receptor for a ketone body, β-hydroxybutyric acid (BHB), and is coupled with Gi-GTP binding protein. HCA(2) expression was reported in the guinea pig heart. Therefore, using guinea pig cardiac myocytes, we investigated effects of BHB on L-type Ca(2+) current pre-augmented with β-adrenoceptor agonist, isoproterenol under the whole-cell voltage clamp. BHB significantly reduced the Ca(2+) current pre-augmented with isoproterenol. The effect of BHB was concentration dependent with IC(50) of 1.1 mM. Nicotinic acid (NA), another ligand for HCA(2), also exerted an effect on the Ca(2+) current similar to that of BHB. The effects of BHB and NA were reduced by a specific Gi inhibitor, pertussis toxin in the pipette solution. Our results suggest that BHB activates Gi-coupled signal transduction pathway via HCA(2) in guinea pig cardiac myocytes. The HCA(2)-mediated signal transduction may be associated with ketoacidosis-induced cardiac suppression.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Fukushima Medical University, Fukushima, Japan. mkuri@fmu.ac.jp
authors.forename: Masato
authors.initials: M
authors.lastname: Kurihara
authors.forename: Youichi
authors.initials: Y
authors.lastname: Akama
authors.forename: Junko
authors.initials: J
authors.lastname: Kimura
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006168:Guinea Pigs; D006331:Heart Diseases / Q000209:etiology / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007657:Ketone Bodies / Q000494:pharmacology; D007662:Ketosis / Q000150:complications / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D009525:Niacin / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D007657:Ketone Bodies; D009525:Niacin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007545:Isoproterenol; D020155:3-Hydroxybutyric Acid