title: Possible involvement of A₂A and A₃ receptors in modulation of insulin secretion and β-cell survival in mouse pancreatic islets.
abstract: Adenosine A1, A₂A, A₂B and A₃ receptor mRNAs were found to be expressed in mouse pancreatic islets and Beta-TC6 cells but their physiological or pharmacological actions are not fully clarified. We showed that adenosine (100 μM) augmented insulin secretion by islets in the presence of either normal (5.5 mM) or a high concentration of glucose (20 mM). The augmentation of insulin secretion in the presence of high glucose was blocked by an A₂A antagonist, but not by A₂B and A₃ antagonists, while an A₁ antagonist potentiated the adenosine effect. An adenosine analogue 5'-N-ethylcarboxamidoadenosine (NECA) as well as A₁, A₂A and A₃ receptor agonists also produced stimulation. On the other hand, an A₃ agonist markedly reduced Beta-TC6 cell proliferation and the islet cell viability, while adenosine and NECA did not. The effect of A₃ agonist was partially blocked by the A₃ antagonist. In addition, treatment with the A₃ agonist produced a small but significant extent of apoptosis in Beta-TC6 cells as judged by terminal transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay. These results combined together suggested that like the A₁ receptor, activation of A₂A receptors by adenosine results in augmented insulin secretion, while the A₃ receptor is involved in modulation of the survival of pancreatic β-cells.
authors: Department of Pharmacology, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan. otani-m@cc.osaka-dent.ac.jp
authors: M
authors: M
authors: Ohtani
authors: T
authors: T
authors: Oka
authors: K
authors: K
authors: Ohura
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D005947:Glucose / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D005947:Glucose; D000241:Adenosine