PD128,907 Induces Ocular Hypotension in Rabbits: Involvement of D₂/D₃ Dopamine Receptors and Brain Natriuretic Peptide

Abstract

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.

Expression of Melatonin and Dopamine D3 Receptor Heteromers in Eye Ciliary Body Epithelial Cells and Negative Correlation with Ocular Hypertension

“…A prospection study, made in our laboratory, showed the expression of the D 3 R in different cells of the eye structure, including those that controlled IOP. These expression results fit with pharmacological studies showing that different D 3 R agonists may lower IOP and that the effect is lost in D 3 R -/mice [43][44][45]. From earlier studies by the laboratory of S. George [55][56][57] it is known that dopamine receptors may directly interact with themselves to form homodimers or with other GPCRs.…”

“…Dopamine D 4 receptors were detected in the vertebrate retina [41] and D 2 and D 3 receptors were identified in the human retina by targeted mass spectrometry and positron emission tomography [42]. Indirect evidence based on pharmacological assays and on responses in D 3 receptor (D 3 R) KO mice showed that D 3 R activation leads to IOP reduction [43][44][45]. In preliminary experiments, we have detected the D 3 receptor in human ciliary body epithelial cells.…”

A comparative study of topical natural ergot alkaloids on the intraocular pressure and aqueous humor dynamics in oclular normotensive and α-chymotrypsin-induced ocular hypertensive rabbits

“…Dopamine receptors D 1 and D 2 appear to play a role in the regulation of intraocular pressure in rabbits [32]. Whereas activation of D 1 dopamine receptors has been generally shown to cause a rise in intraocular pressure, probably by increasing aqueous humor production [20], D 2 agonists have been found to lower intraocular pressure by reducing aqueous humor inflow [9,41]. It has been reported in humans that NPE cells possess dopamine D 1 receptors linked to the Na + K + 2Cl − co-transporter involved in aqueous humor formation [18].…”

Short-Term Effect of Acupuncture on Intraocular Pressure in Healthy Subjects

“…2 Experimental studies have demonstrated a hypotensor ocular effect of acupuncture in rabbits and dogs. [3][4][5] Previous studies in humans have also described intraocular pressure (IOP) reduction. 6 7 Chu and Potter (2002) hypothesised that acupuncture could reduce the aqueous humour fl ow rate through an endogenous mechanism, possibly by an induced decrease of catecholamine levels.…”