title: Functional characterization of the adenosine receptor contributing to glycogenolysis and gluconeogenesis in rat hepatocytes.
abstract: The adenosine receptor subtype mediating glucose production by glycogenolysis and gluconeogenesis was studied in primary cultured rat hepatocytes. Adenosine and adenosine agonists caused cyclic AMP accumulation in rat hepatocytes. The order of potency was 5'-N-ethylcarboxamidoadenosine (NECA)>R(-)-N(6)-(2-phenylisopropyl)adenosine (RPIA)>adenosine>2-[p-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680). Furthermore, adenosine agonists stimulated glycogenolysis and gluconeogenesis. The order of potency was NECA>RPIA>CGS21680. The rank order of potency is typical for adenosine A(2B) receptors. Glycogenolysis stimulated by NECA was fully inhibited by nonselective adenosine antagonists, 9-chloro-2-(2-furanyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (CGS15943). However, the adenosine A(2A) receptor-selective antagonist, 8-(3-chlorostyryl)caffeine (CSC), and the adenosine A(1) receptor-selective antagonist, (+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-alpha]pyridin-3-yl)acryloyl]-2-piperidine ethanol (FK453), had a low inhibitory potency. A strong correlation was found between the inhibitory effect of adenosine antagonists on NECA-induced glucose production and that on intracellular cyclic AMP generation in rat hepatocytes. Our results suggest that adenosine stimulates cyclic AMP formation and regulates glycogenolysis and gluconeogenesis, most likely through the adenosine A(2B) receptor subtype in rat hepatocytes.
authors.affiliation: Tsukuba Research Laboratories, Eisai Co. Ltd., 5-1-3 Tokodai, Ibaraki 300-2635, Tsukuba, Japan. n-yasuda@hhc.eisai.co.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yasuda
authors.forename: Takashi
authors.initials: T
authors.lastname: Inoue
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Horizoe
authors.forename: Kaya
authors.initials: K
authors.lastname: Nagata
authors.forename: Hiroe
authors.initials: H
authors.lastname: Minami
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kawata
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Harada
authors.forename: Seiji
authors.initials: S
authors.lastname: Yoshikawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Asano
authors.forename: Junsaku
authors.initials: J
authors.lastname: Nagaoka
authors.forename: Manabu
authors.initials: M
authors.lastname: Murakami
authors.forename: Shinya
authors.initials: S
authors.lastname: Abe
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Isao
authors.initials: I
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005943:Gluconeogenesis / Q000187:drug effects / Q000502:physiology*; D006003:Glycogen / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
chemical_list: D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D006003:Glycogen