Mechanisms and sites of ocular action of 7-hydroxy-2-dipropylaminotetralin: A Dopamine(3) receptor agonist

The purpose of this study was to investigate mechanism(s) and site(s) of ac tion involved in 7-hydroxy-2-dipropylaminotetralin (7-OH-DPAT)-induced ocul ar hypotension. As measured by pneumatonometry, the topical, unilateral app lication of 7-OH-DPAT (75 mu g), a dopamine D-3-preferring receptor agonist , decreased the intraocular pressure (IOP) bilaterally. The ocular hypotens ive activity of 7-OH-DPAT was diminished in sympathetically denervated rabb its. Pretreatment with raclopride, a D-2/D-3 receptor antagonist; UH232, a D-3 receptor antagonist; or U-99194A, a D-3 receptor antagonist antagonized 7-OH-DPAT-induced ocular hypotension. However, pretreatment with spiperone , a D-2 receptor antagonist, did not affect the 7-OH-DPAT-induced ocular hy potension. In addition, topically applied 7-OH-DPAT caused a reduction of a queous humor flow rate. To examine sites of action, immunohistochemistry of D-3 dopamine receptors was performed. Dopamine D-3 receptors were found to be present on postganglionic sympathetic nerves in the ciliary body of nor mal rabbits but were virtually undetectable in the same tissue of sympathec tomized rabbits. In summary, the IOP-lowering effect caused by 7-OH-DPAT wa s due, in part, to the suppression of aqueous humor flow. Immunohistochemic al identification of D-3 receptors in the ciliary body, associated with the diminution of IOP-lowering effects by D-3 receptor agonist 7-OH-DPAT in sy mpathetically denervated rabbits provided evidence of neuronal site of acti on of 7-OH-DPAT. Suppression of 7-OH-DPAT-induced ocular hypotension by D-3 receptor antagonists (U-99194A and UH232) and sympathectomy, coupled with the immunohistochemical data, suggested that the primary site of D-3 recept or-mediated action of 7-OH-DPAT is located on postganglionic sympathetic ne rve endings in the ciliary body of rabbit.