Adenosine A2A receptor mediated protective effect of 2-(6-cyano-1-hexyn-1-yl)adenosine on retinal ischaemia/reperfusion damage in rats
- 1Drug Research Section II, Fukushima Research Laboratories, Toa Eiyo Ltd, Fukushima, Japan
- 2Department of Cellular Signaling and 21st Century COE program “CRESCENDO”, Graduate School of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan
- Correspondence to: Takashi Konno Drug Research Section II, Fukushima Research Laboratories, Toa Eiyo Ltd, 1 Tanaka, Yuno, Iizaka, Fukushima 960-0280, Japan; konno.takashi{at}toaeiyo.co.jp
- Accepted 4 March 2006
- Published Online First 13 April 2006
Abstract
Aims: To determine the effect of 2-(6-cyano-1-hexyn-1-yl)adenosine (2-CN-Ado), an adenosine A2A receptor agonist, on retinal ischaemia/reperfusion damage in rats.
Methods: Retinal ischaemia/reperfusion damage was induced by elevating the intraocular pressure of one eye to 130 mm Hg for 60 minutes and returning it to normal. 7 days later, retinal ischaemia/reperfusion damage was histologically quantified by measuring the thickness of retinal layers. Intraocular pressure was measured by pressure transducer.
Results: Retinal ischaemia/reperfusion caused cell loss in the ganglion cell layer and thinning of the inner plexiform and nuclear layer. Both ocular topical and intravenous administration of 2-CN-Ado caused a reduction of retinal ischaemia/reperfusion damage. A selective A2A receptor antagonist, 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine (CSC), but not a selective A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or a selective A2B receptor antagonist, alloxazine, reduced the protective effect of 2-CN-Ado. While ocular topical administration of 2-CN-Ado caused a sustained reduction of intraocular pressure, intravenous administration of 2-CN-Ado showed a transient ocular hypotensive effect.
Conclusions: These results suggest that 2-CN-Ado attenuates retinal ischaemia/reperfusion damage, and at least some of this protective effect of 2-CN-Ado might be mediated via activation of the adenosine A2A receptor.
- CGS-21680, 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine
- 2-CN-Ado, 2-(6-cyano-1-hexyn-1-yl)adenosine
- CSC, 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine
- DMSO, dimethyl sulfoxide
- DPCPX, 8-cyclopentyl-1,3-dipropylxanthine
- ip, intraperitonal
- IPL, inner plexiform layer
- IRL, inner retinal layer
- iv, intravenous
- NMDA, N-methyl-d-aspartate
- ONH, optic nerve head
- 2-alkynyladenosine derivatives
- adenosine A2A receptor
- ischaemia
- reperfusion damage
- retina
- intraocular pressure
- rat
- CGS-21680, 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine
- 2-CN-Ado, 2-(6-cyano-1-hexyn-1-yl)adenosine
- CSC, 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine
- DMSO, dimethyl sulfoxide
- DPCPX, 8-cyclopentyl-1,3-dipropylxanthine
- ip, intraperitonal
- IPL, inner plexiform layer
- IRL, inner retinal layer
- iv, intravenous
- NMDA, N-methyl-d-aspartate
- ONH, optic nerve head
- 2-alkynyladenosine derivatives
- adenosine A2A receptor
- ischaemia
- reperfusion damage
- retina
- intraocular pressure
- rat
Footnotes
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Competing interests: none.









