Involvement of Adenosine A2a Receptor in Intraocular Pressure Decrease Induced by 2-(1-Octyn-1-yl)adenosine or 2-(6-Cyano-1-hexyn-1-yl)adenosine
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概要
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The aim of the present study is to clarify the mechanism for the decrease in intraocular pressure by 2-alkynyladenosine derivatives in rabbits. The receptor binding analysis revealed that 2-(1-octyn-1-yl)adenosine (2-O-Ado) and 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado) selectively bound to the A2a receptor with a high affinity. Ocular hypotensive responses to 2-O-Ado and 2-CN-Ado were inhibited by the adenosine A2a-receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), but not by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or the adenosine A2b-receptor antagonist alloxazine. In addition, 2-O-Ado and 2-CN-Ado caused an increase in outflow facility, which was inhibited by CSC, but not by DPCPX or alloxazine. Moreover, 2-O-Ado and 2-CN-Ado increased cAMP in the aqueous humor, and the 2-O-Ado-induced an increase in cAMP was inhibited by CSC. These results suggest that 2-O-Ado and 2-CN-Ado reduced intraocular pressure via an increase in outflow facility. The ocular hypotension may be mailnly mediated through the activation of adenosine A2a receptor, although a possible involvement of adenosine A1 receptor cannot be completely ruled out. 2-O-Ado and 2-CN-Ado are useful lead compounds for the treatment of glaucoma.
著者
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Nakahata Norimichi
Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Jap
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Konno Takashi
Drug Research Section Ii Fukushima Research Laboratories Toa Eiyo Ltd.
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Murakami Akira
Drug Research Section I Tokyo Research Laboratories Toa Eiyo Ltd.
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Kogi Kentaro
Drug Research Section Ii Fukushima Research Laboratories Toa Eiyo Ltd.
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Nakahata Norimichi
Department Of Cellular Signaling And 21st Century Coe Program Graduate School Of Pharmaceutical Scie
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Nagai Akihiko
Drug Research Section Ii Fukushima Research Laboratories Toa Eiyo Ltd.
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UCHIBORI Takehiro
Drug Research Section II, Fukushima Research Laboratories, Toa Eiyo Ltd.
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Uchibori Takehiro
Drug Research Section Ii Fukushima Research Laboratories Toa Eiyo Ltd.
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NAKAHATA Norimichi
Department of Cellular Signaling and 21st Century COE Program, Graduate School of Pharmaceutical Sciences, Tohoku University
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MURAKAMI Akira
Drug Research Section I, Tokyo Research Laboratories, Toa Eiyo Ltd.
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