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J. Biol. Chem., Vol. 280, Issue 31, 28556-28563, August 5, 2005

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Dual Roles of P2 Purinergic Receptors in Insulin-stimulated Leptin Production and Lipolysis in Differentiated Rat White Adipocytes^*

Hyun Lee, Dong-Jae Jun, Byung-Chang Suh, Bo-Hwa Choi, Jong-Hee Lee, Myoung-Sool Do¶, Byung-Sun Suh¶, Hyunjung Ha||, and Kyong-Tai Kim**

From the Department of Life Science, Pohang University of Science and Technology, Pohang 790-784, the ^¶School of Bioscience and Food Technology, Handong Global University, Pohang 791-940, and the ^||Department of Biochemistry, School of Life Science, Chungbuk National University, Cheongju 361-736, Korea

ATP is co-localized with norepinephrine at the sympathetic nerve terminals and may be released simultaneously upon neuronal stimulation, which results in activation of purinergic receptors. To examine whether leptin synthesis and lipolysis are influenced by P2 purinergic receptor activation, the effects of ATP and other nucleotides on leptin secretion and glycerol release have been investigated in differentiated rat white adipocytes. Firstly, insulin-induced leptin secretion was inhibited by nucleotide treatment with the following efficacy order: 3'-O-(4-benzoyl)benzoyl ATP (BzATP) > ATP >> UTP. Secondly, treatment of adipocytes with ATP increased both intracellular Ca²⁺ concentration and cAMP content. Intracellular calcium concentration was increased by ATP and UTP, but not BzATP, an effect attributed to phospholipase C-coupled P2Y₂. On the other hand, cAMP was generated by treatment with BzATP and ATPS, but not UTP, indicating functional expression of adenylyl cyclase-coupled P2Y₁₁ receptors in white adipocytes. Thirdly, lipolysis was significantly activated by BzATP and ATP, which correlated with the characteristics of the P2Y₁₁ subtype. Taken together, the data presented here suggest that white adipocytes express at least two different types of P2Y receptors and that activation of P2Y₁₁ receptor might be involved in inhibition of leptin production and stimulation of lipolysis, suggesting that purinergic transmission can play an important role in white adipocyte physiology.

Received for publication, October 1, 2004 , and in revised form, June 10, 2005.

^* This work was supported by grants from the National Research Laboratory Program (2000-N-NL-01-C-150), Brain Neurobiology Research Program (M10108000013-02B2300-00710) of the Ministry of Science and Technology (MOST), the Korea Science and Engineering Foundation (KOSEF; R01-1999-000-00145-0), IMT2000 Fund from the Ministry of Health and Welfare and, Brain Korea 21 program of the Ministry of Education. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains Supplemental Figs. S1 and S2.

Both authors contributed equally to this work.

^** To whom correspondence should be addressed. Tel.: 82-54-279-2297; Fax: 82-54-279-2199; E-mail: ktk{at}postech.ac.kr.

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