Adenosine receptor activation modulates intraocular pressure in rabbits
Crosson, C.E.
Journal of Pharmacology and Experimental Therapeutics 273(1): 320-326
1995
ISSN/ISBN: 0022-3565 PMID: 7714784 Document Number: 440002
The relatively selective adenosine A-1 agonists N-6-cyclohexyladenosine (CHA), R(-)-N-6-(2-phenylisopropyl)adenosine (RPIA) and S(+)-N-6-(2-phenylisopropyl)adenosine (S-PIA); the A-2a agonist 2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamidoadenosine (CGS-21680) and the nonselective A-2 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 gt CGS-21680 gt S-PIA gt 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 A-1 receptors. This response is associated with a reduction in aqueous flow and the modulation of cAMP in the iris/ciliary body. Although the CV-1808-induced rise in IOP also appears to result from the activation of adenosine receptors, determination of the receptor subtype and mechanism of action involved in this response requires additional investigation.