2-(1-Hexyn-1-yl)adenosine-induced intraocular hypertension is mediated via K+ channel opening through adenosine A2A receptor in rabbits.
The present study was performed to clarify the mechanism of change in intraocular pressure by 2-(1-hexyn-1-yl)adenosine (2-H-Ado), a selective adenosine A2 receptor agonist, in rabbits. 2-H-Ado (0.1%, 50 microl)-induced ocular hypertension (E(max): 7.7 mm Hg) was inhibited by an adenosine A2A receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine, ATP-sensitive K+ channel blocker glibenclamide or 5-hydroxydecanoic acid, but not by an adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A2B receptor antagonist alloxazine or a cyclooxygenase inhibitor indomethacin. The outflow facility induced by 2-H-Ado seems to be independent of increase in intraocular pressure or ATP-sensitive K+ channel. In contrast, the recovery rate in intraocular pressure decreased by hypertonic saline was accelerated by 2-H-Ado, and this response was dependent on ATP-sensitive K+ channel. These results suggest that 2-H-Ado-induced ocular hypertension is mediated via K+ channel opening through adenosine A2A receptor, and this is probably due to aqueous formation, but independent of change in outflow facility or prostaglandin production.
Konno
Takashi
T
Drug Research Section II, Fukushima Research Laboratories, Toa Eiyo Ltd., Iizaka, Fukushima 960-0280, Japan. konno.takashi@toaeiyo.co
Uchibori
Takehiro
T
Nagai
Akihiko
A
Kogi
Kentaro
K
Nakahata
Norimichi
N
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D003652:Decanoic Acids / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D006880:Hydroxy Acids / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009798:Ocular Hypertension / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D010627:Phenethylamines / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D013997:Time Factors; D014970:Xanthines / Q000494:pharmacology
D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000480:Alkynes; D000959:Antihypertensive Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D007038:Hypotonic Solutions; D010627:Phenethylamines; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D043705:Receptor, Adenosine A2A; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C081320:8-(3-chlorostyryl)caffeine; D002110:Caffeine; C048599:N(6)-cyclopentyladenosine; D012965:Sodium Chloride; C052853:5-hydroxydecanoic acid; D020110:Pinacidil; C070493:2-hexynyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D005905:Glyburide