Abstract |
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 A(2a) receptor with a high affinity. Ocular hypotensive responses to 2-O-Ado and 2-CN-Ado were inhibited by the adenosine A(2a)-receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC), but not by the adenosine A(1)-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine ( DPCPX) or the adenosine A(2b)-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 mainly mediated through the activation of adenosine A(2a) receptor, although a possible involvement of adenosine A(1) receptor cannot be completely ruled out. 2-O-Ado and 2-CN-Ado are useful lead compounds for the treatment of glaucoma.
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Authors | Takashi Konno, Akira Murakami, Takehiro Uchibori, Akihiko Nagai, Kentaro Kogi, Norimichi Nakahata |
Journal | Journal of pharmacological sciences
(J Pharmacol Sci)
Vol. 97
Issue 4
Pg. 501-9
(Apr 2005)
ISSN: 1347-8613 [Print] Japan |
PMID | 15821340
(Publication Type: Journal Article)
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Chemical References |
- 2-(6-cyano-1-hexyn-1-yl)adenosine
- Alkynes
- Receptor, Adenosine A2A
- YT 146
- Cyclic AMP
- Adenosine
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Topics |
- Adenosine
(analogs & derivatives, metabolism, pharmacology)
- Alkynes
(metabolism, pharmacology)
- Animals
- Aqueous Humor
(drug effects, metabolism)
- Cyclic AMP
(metabolism)
- Glaucoma
(drug therapy)
- Humans
- Intraocular Pressure
(drug effects, physiology)
- Kinetics
- Male
- Rabbits
- Receptor, Adenosine A2A
(drug effects, metabolism, physiology)
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