Functional characterization of the adenosine receptor contributing to glycogenolysis and gluconeogenesis in rat hepatocytes.
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.
Yasuda
Nobuyuki
N
Tsukuba Research Laboratories, Eisai Co. Ltd., 5-1-3 Tokodai, Ibaraki 300-2635, Tsukuba, Japan. n-yasuda@hhc.eisai.co.jp
Inoue
Takashi
T
Horizoe
Tatsuo
T
Nagata
Kaya
K
Minami
Hiroe
H
Kawata
Tsutomu
T
Hoshino
Yorihisa
Y
Harada
Hitoshi
H
Yoshikawa
Seiji
S
Asano
Osamu
O
Nagaoka
Junsaku
J
Murakami
Manabu
M
Abe
Shinya
S
Kobayashi
Seiichi
S
Tanaka
Isao
I
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*
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D006003:Glycogen