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Research ArticleNEUROPHARMACOLOGY

Mechanisms and Sites of Ocular Action of 7-Hydroxy-2-dipropylaminotetralin: A Dopamine3 Receptor Agonist

Eugenia Chu, Teh-Ching Chu and David E. Potter
Journal of Pharmacology and Experimental Therapeutics June 2000, 293 (3) 710-716;
Eugenia Chu
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Teh-Ching Chu
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David E. Potter
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Abstract

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.

Footnotes

  • Send reprint requests to: Teh-Ching Chu, Ph.D. Department of Pharmacology and Toxicology, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA 30310-1495. E-mail: tc{at}msm.edu

  • ↵1 This study was supported, in part, by National Institutes of Health Grants EY11977 (to D.E.P.) and S06GM08248-12 (to T.C.C.).

  • Abbreviations:
    IOP
    intraocular pressure
    TNPA
    R-(−)-2,10,11-trihydroxy-N-propyl-noraporphine hydrobromide
    7-OH-DPAT
    7-hydroxy-2-dipropylaminotetralin
    U-99194A
    5,6-dimethoxy-2 (di-n-propylamino) indan
    UH232
    cis-(+)-5-methoxy-1-methyl-2-(di-n-propylamino) tetralin
    FITC
    fluorescein isothiocyanate
    • Received December 21, 1999.
    • Accepted March 2, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 293 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 293, Issue 3
1 Jun 2000
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Research ArticleNEUROPHARMACOLOGY

Mechanisms and Sites of Ocular Action of 7-Hydroxy-2-dipropylaminotetralin: A Dopamine3 Receptor Agonist

Eugenia Chu, Teh-Ching Chu and David E. Potter
Journal of Pharmacology and Experimental Therapeutics June 1, 2000, 293 (3) 710-716;

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Research ArticleNEUROPHARMACOLOGY

Mechanisms and Sites of Ocular Action of 7-Hydroxy-2-dipropylaminotetralin: A Dopamine3 Receptor Agonist

Eugenia Chu, Teh-Ching Chu and David E. Potter
Journal of Pharmacology and Experimental Therapeutics June 1, 2000, 293 (3) 710-716;
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