Adenosine receptor activation modulates intraocular pressure in rabbits.
The relatively selective adenosine A1 agonists N6-cyclohexy-ladenosine (CHA), R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA) and S(+)-N6-(2-phenylisopropyl)adenosine (S-PIA); the A2a agonist 2-p-carboxyethyl)phenethyl-amino-5'-N-ethylcarbox-amidoadenosin e (CGS-21680) and the nonselective A2 agonist 2-phenylaminoadenosine (CV-1808) were evaluated in vivo for their effects on aqueous humor dynamics and in vitro for their action on 3H-norepinephrine release and cAMP accumulation in the isolated iris/ciliary body. These studies demonstrated that adenosine agonists can modulate intraocular pressure (IOP). Except for CV-1808, the topical administration of adenosine agonists produced a unilateral dose-related reduction in IOP with a potency order of R-PIA = CHA > CGS-21680 > S-PIA > CV-1808. Although CV-1808 did not lower IOP, it did induce a significant dose-dependent rise in IOP. Neither the reduction in IOP induced by R-PIA nor the rise in IOP induced by CV-1808 was affected by surgical removal of the superior cervical ganglion. However, the adenosine agonist-induced reduction in IOP was associated with a significant decrease in aqueous flow. In vitro studies demonstrated that the adenosine agonists did not alter the evoked release of 3H-norepinephrine; however, they were effective in suppressing the accumulation of cAMP, and this response was blocked by pretreatment with the antagonist 8-cyclopentyl-1,3-dimethylxanthine. These studies provide evidence that adenosine agonists lower IOP by activating postjunctional adenosine A1 receptors. This response is associated with a reduction in aqueous flow and the modulation of cAMP in the iris/ciliary body.(ABSTRACT TRUNCATED AT 250 WORDS)
Crosson
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Department of Ophthalmology and Visual Sciences, Texas Tech University Health Sciences Center, Lubbock, USA.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000096:biosynthesis; D007429:Intraocular Pressure / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D010660:Phenylisopropyladenosine; C027513:N(6)-cyclohexyladenosine; D000242:Cyclic AMP; C026708:2-phenylaminoadenosine; D000241:Adenosine; D009638:Norepinephrine