title: Dopamine-₃ receptor modulates intraocular pressure: implications for glaucoma.
abstract: The aim of the present study was to investigate the role of D₃ receptor on intraocular pressure regulation using WT and KO D₃R⁻/⁻ mice. Both mice were used with normal eye pressure or steroid-induced ocular hypertension. As measured by tonometry, the topical application of 7-OH-DPAT, a dopamine D₃-preferring receptor agonist, significantly decreased, in a dose-dependent manner, the intraocular pressure in WT mice both in an ocular normotensive group and an ocular hypertensive group. Pretreatment with U-99194A, a D₃ receptor antagonist, reverted 7-OH-DPAT induced ocular hypotension in WT mice. No change of intraocular pressure was observed after topical application of 7-OH-DPAT in KO D₃R⁻/⁻ mice. PCR analysis demonstrated the presence of all dopamine receptor genes in eye tissues obtained from WT mice, and the lack of D₃R mRNAs in KO mice. The present study identified the D₃R subtype as the most important receptor of the dopaminergic system to modulate intraocular pressure with relevant implications for glaucoma that represents one of the most crippling optic neuropathies.
authors.affiliation: Section of Pharmacology and Biochemistry, Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy. claudio.bucolo@unict.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Bucolo
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Leggio
authors.forename: Adriana
authors.initials: A
authors.lastname: Maltese
authors.forename: Alessandro
authors.initials: A
authors.lastname: Castorina
authors.forename: Velia
authors.initials: V
authors.lastname: D'Agata
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005901:Glaucoma / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D007189:Indans / Q000494:pharmacology; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
chemical_list: D018491:Dopamine Agonists; D007189:Indans; D012333:RNA, Messenger; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin