RT Journal Article SR Electronic T1 Mechanisms and Sites of Ocular Action of 7-Hydroxy-2-dipropylaminotetralin: A Dopamine3 Receptor Agonist JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 710 OP 716 VO 293 IS 3 A1 Chu, Eugenia A1 Chu, Teh-Ching A1 Potter, David E. YR 2000 UL http://jpet.aspetjournals.org/content/293/3/710.abstract AB The purpose of this study was to investigate mechanism(s) and site(s) of action involved in 7-hydroxy-2-dipropylaminotetralin (7-OH-DPAT)-induced ocular hypotension. As measured by pneumatonometry, the topical, unilateral application of 7-OH-DPAT (75 μg), a dopamine D3-preferring receptor agonist, decreased the intraocular pressure (IOP) bilaterally. The ocular hypotensive activity of 7-OH-DPAT was diminished in sympathetically denervated rabbits. Pretreatment with raclopride, a D2/D3receptor antagonist; UH232, a D3 receptor antagonist; or U-99194A, a D3 receptor antagonist antagonized 7-OH-DPAT-induced ocular hypotension. However, pretreatment with spiperone, a D2 receptor antagonist, did not affect the 7-OH-DPAT-induced ocular hypotension. In addition, topically applied 7-OH-DPAT caused a reduction of aqueous humor flow rate. To examine sites of action, immunohistochemistry of D3 dopamine receptors was performed. Dopamine D3 receptors were found to be present on postganglionic sympathetic nerves in the ciliary body of normal rabbits but were virtually undetectable in the same tissue of sympathectomized rabbits. In summary, the IOP-lowering effect caused by 7-OH-DPAT was due, in part, to the suppression of aqueous humor flow. Immunohistochemical identification of D3 receptors in the ciliary body, associated with the diminution of IOP-lowering effects by D3 receptor agonist 7-OH-DPAT in sympathetically denervated rabbits provided evidence of neuronal site of action of 7-OH-DPAT. Suppression of 7-OH-DPAT-induced ocular hypotension by D3receptor antagonists (U-99194A and UH232) and sympathectomy, coupled with the immunohistochemical data, suggested that the primary site of D3 receptor-mediated action of 7-OH-DPAT is located on postganglionic sympathetic nerve endings in the ciliary body of rabbit. The American Society for Pharmacology and Experimental Therapeutics