n(6)-cyclopentyladenosine and 8-(3-chlorostyryl)caffeine

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.

Topics: Adenosine; Adenosine A2 Receptor Agonists; Adenosine A2 Receptor Antagonists; Alkynes; Animals; Antihypertensive Agents; Caffeine; Decanoic Acids; Glyburide; Hydroxy Acids; Hypotonic Solutions; Intraocular Pressure; Male; Ocular Hypertension; Phenethylamines; Pinacidil; Potassium Channel Blockers; Potassium Channels; Rabbits; Receptor, Adenosine A2A; Sodium Chloride; Time Factors; Xanthines

This study was performed to determine whether intravitreal or intravenous adenosine can alter the microcirculation in the optic nerve head (ONH) of rabbits. Capillary blood flow in the ONH was measured serially with a laser speckle tissue analyser for 2 hr after the intravitreal (0.1, 1.0 and 10 nmol) or intravenous (0.2 and 0.6 mg kg(-1)min) injections of adenosine. In addition, the effect of specific adenosine A(1) and A(2a) antagonists and an adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channel blockers on the adenosine-induced changes on the ONH blood flow was analysed. Intravitreal adenosine increased the capillary blood flow in the ONH in a dose-dependent manner, while intravenous adenosine had no effect. Co-administration of the specific adenosine A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nmol) significantly suppressed (P=0.006, ANOVA) the increase in the ONH blood flow induced by adenosine (10 nmol). The specific A(2a) receptor antagonist, 8-(3-chlorostyryl) caffeine (CSC, 10 nmol), had a weak effect in inhibiting the increase but the change was not significant (P=0.08, ANOVA). Both specific A(1) and A(2a) receptor agonists, N(6)-cyclopentyladenosine (CPA, 10 nmol) and 2-p-(2-carboxyethyl) phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680, 10 nmol), increased the ONH tissue blood flow (P<0.01, ANOVA). Glibenclamide (10 nmol), a selective K(ATP) channels antagonist, suppressed the increase of ONH blood flow induced by 10 nmol adenosine significantly (P<0.001, ANOVA). On the other hand, 10 nmol of 8-Br-cAMP, a cAMP analog, failed to enhance the capillary blood flow in the ONH. These results indicate that adenosine increases the capillary blood flow in the ONH of rabbits, and it acts through A(1) and A(2a) receptors from the ablumenal side where pericytes are located. Activation of K(ATP) channels is strongly related to the mechanism of adenosine-induced increase in ONH blood flow, while the participation of adenylate cyclase is less likely.

Topics: 8-Bromo Cyclic Adenosine Monophosphate; Adenosine; Adenosine A1 Receptor Antagonists; Adenylyl Cyclase Inhibitors; Animals; Caffeine; Capillaries; Dose-Response Relationship, Drug; Glyburide; Injections; Injections, Intravenous; Optic Disk; Phenethylamines; Potassium Channels; Purinergic P1 Receptor Agonists; Purinergic P2 Receptor Antagonists; Rabbits; Regional Blood Flow; Stimulation, Chemical; Vasodilation; Vitreous Body; Xanthines