Modulation of intraocular pressure by adenosine agonists.

Adenosine receptors have been shown to modulate a variety of physiological functions; however, little is known about the role these receptors play in the modulation of ocular function. To investigate the potential role of adenosine receptors in modulating intraocular pressure (IOP), the A1 agonist N6-cyclopentyladenosine (CPA), the nonselective adenosine agonist 5'-N-ethylcarboxamideadenosine (NECA) and the A2 agonist 8-phenylaminoadenosine (CV-1808) were evaluated. Topical administration of NECA produced a dose-related reduction in IOP. However, an initial ocular hypertension of 1 to 2 hours was also observed in rabbits treated with NECA. The administration of CPA (165 micrograms) resulted only in a reduction in IOP, while the administration of CV-1808 produced only an initial ocular hypertension. As adenosine A1 receptors have been shown to be negatively coupled to adenylate cyclase in several systems, CPA was evaluated for its ability to suppress cAMP formation in the isolated iris/ciliary body. CPA produced a dose-related suppression of cAMP accumulation induced by 10(-6) M forskolin (EC50 = 3.2 nM). These results indicate that selected adenosine agonists can modulate IOP. The ocular hypotension induced by adenosine agonists is consistent with the activation of adenosine A1 receptors and may involve the modulation of cAMP levels in the iris/ciliary body.