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

• Published in: Journal of Pharmacological Sciences Vol. 97; no. 4; pp. 501 - 509
• Main Authors: Konno, Takashi, Murakami, Akira, Uchibori, Takehiro, Nagai, Akihiko, Kogi, Kentaro, Nakahata, Norimichi
• Format: Journal Article
• Language: English; Japanese
• Published: Japan Elsevier B.V 2005; The Japanese Pharmacological Society; Elsevier
• Subjects: 2-alkynyladenosine derivative; Adenosine - analogs & derivatives; Adenosine - metabolism; Adenosine - pharmacology; adenosine A2a receptor; Alkynes - metabolism; Alkynes - pharmacology; Animals; Aqueous Humor - drug effects; Aqueous Humor - metabolism; cAMP; Cyclic AMP - metabolism; Glaucoma - drug therapy; Humans; intraocular pressure; Intraocular Pressure - drug effects; Intraocular Pressure - physiology; Kinetics; Male; outflow facility; Rabbits; Receptor, Adenosine A2A - drug effects; Receptor, Adenosine A2A - metabolism; Receptor, Adenosine A2A - physiology; outflow facility; adenosine A2a receptor; intraocular pressure; cAMP; 2-alkynyladenosine derivative
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1254/jphs.fp0040730

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.