Adenylyl cyclase P-site ligands accelerate differentiation in Ob1771 preadipocytes |
| |
Authors: | Ibrahimi, Azeddine Abumrad, Nada Maghareie, Hengameh Golia, Michael Shoshani, Ilana Desaubry, Laurent Johnson, Roger A. |
| |
Abstract: | Differentiation of Ob1771 preadipocytes to adipocytes wascharacterized by morphological changes and elevated expression of thespecific marker enzyme, glycerol-3-phosphate dehydrogenase. Adifferentiation response substantially more complete and rapid thanthat obtained with insulin and 3,5,3'-triiodothyronine was observed with established inhibitors of adenylyl cyclases:2',5'-dideoxyadenosine (2',5'-dd-Ado),9-(cyclopentyl)adenine (9-CP-Ade), and 9-(arabinofuranosyl)adenine (9-Ara-Ade), coincident with decreased cellular cAMP levels. These ligands inhibit adenylyl cyclases noncompetitively, via a domain referred to as the P-site because of its requirement for an intact purine moiety. Differentiation was not induced by inosine, a nucleoside known not to act at the P-site, or byN6-(2-phenylisopropyl)adenosineor 1,3-diethyl-8-phenylxanthine, agonist and antagonist, respectively,for adenosine A1 receptors. Alsoineffective were IBMX or forskolin, agents that can raise intracellularcAMP levels. Potency of the differentiation response followed the order2',5'-dd-Ado (1-20 µM) > 9-CP-Ade (10-100µM) = 9-Ara-Ade (10-100 µM) >> inosine, consistent withtheir potencies to inhibit adenylyl cyclases. The data suggest thatinhibition of adenylyl cyclase via the P-site and the consequentreduction in cell cAMP levels facilitate the induction ofdifferentiation in Ob1771 cells. The findings raise the questionwhether the known endogenous P-site ligands participate in thedifferentiation response induced by hormones. |
| |
Keywords: | |
|
| 点击此处可从《American journal of physiology. Cell physiology》浏览原始摘要信息 |
|
点击此处可从《American journal of physiology. Cell physiology》下载全文 |
|