PD128,907 induces ocular hypotension in rabbits: involvement of D2/D3 dopamine receptors and brain natriuretic peptide.
The purpose of this study was to determine the potential role of brain natriuretic peptide (BNP) in the PD128,907 (a dopamine D2/D3 receptor agonist)-induced ocular hypotension in rabbits. The effects of topical application of PD128,907 (75, 250, 750 microg) on intraocular pressure (IOP) were investigated. The lowest dose (75 microg) did not alter IOP; while the higher doses (250 and 750 microg) reduced IOP bilaterally. The PD128,907 (250 microg)-induced ocular hypotension, which lasted 3 hours, could be blocked by raclopride (1000 microg), a dopamine D2/D3 receptor antagonist, as well as by sympathetic denervation. Aqueous humor inflow was reduced by intravitreal injection of PD128,907 (10 microg) by 67% at 1 and 2 hours, which then returned to baseline at 3 hours. Furthermore, topical application of PD128,907 (250 microg) elevated aqueous BNP levels by 3-fold at 30 minutes, 6-fold at 1 hour and 5-fold at 2 hours, which could be blocked by pretreatment with raclopride (250 microg). Taken together, PD128,907-induced ocular hypotension by activation of dopamine D2/D3 receptors. This action was associated with reduced aqueous humor inflow and increased aqueous BNP levels.
University of Georgia, Athens, GA, USA.
Eugenia
E
Chu
Robin
R
Socci
Teh-Ching
TC
Chu
D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D015814:Ocular Hypotension / Q000139:chemically induced* / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology*; D011817:Rabbits; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3
D001578:Benzopyrans; D018491:Dopamine Agonists; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020097:Natriuretic Peptide, Brain; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol