Skip to main content
SpringerLink
Log in

Effects of dopamine D-1 and D-2 receptors on intraocular pressure in conscious rabbits

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

This investigation was designed as a randomized, placebocontrolled, double-masked, crossover study in NZW rabbits with normal intraocular pressure (IOP) to investigate dopaminergic effects on IOP. SKF 38393, a selective D1-receptor agonist, increased, and SDZ PSD-958, a selective D1-receptor antagonist, decreased IOP, respectively. The selective D2-receptor agonist quinpirole decreased IOP, whereas the selective D2 receptor antagonist metoclopramide had no significant effect. Combinations of quinpirole with SDZ PSD-958 decreased IOP in an additive manner. SDZ GLC-756, a mixed D1-receptor antagonist/D2-receptor agonist, decreased IOP in a dose-dependent manner with a maximum effect greater than the maximum effects produced either by the D1-receptor antagonist SDZ PSD-958 and the D2-receptor agonist quinpirole. The effect of SDZ GLC-756 could only be partially blocked by the selective D2-receptor antagonist metoclopramide suggesting that both D1-receptor blockade and D2-receptor stimulation participate in its IOP-lowering effect. Tonography suggests that SDZ GLC-756 has no significant effect on outflow facility. Furthermore, the results suggest that both D1 and D2 receptors each play an independent role in the regulation of IOP in rabbits. Thus, simultaneous blockade of D1 receptors and stimulation of D2 receptors may provide a new pharmacological approach for the treatment of ocular hypertension frequently associated with glaucoma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Al-Sereiti MR, Turner P (1989) The effects of lisuride, terguride and bromocriptine on intraocular pressure (IOP). Br J Clin Pharmacol 27: 159–163

    PubMed  Google Scholar 

  • Al-Sereiti MR, Quik RFP, Hedges A, Turner P (1990) Antagonism by domperidone of the ocular hypotensive effect of pergolide. Eur J Clin Pharmacol 38: 461–463

    PubMed  Google Scholar 

  • Becker B, Constant MA (1956) Species variation in facility of aqueous outflow. Am J Ophthalmol 42: 189–194

    Google Scholar 

  • Braun AR, Chase TN (1986) Obligatory D1/D2 receptor interaction in the generation of dopamine agonist related behaviors. Eur J Pharmacol 131: 301–306

    PubMed  Google Scholar 

  • Chiou GCY (1994) Treatment of open angle glaucoma and ischemic retinopathy with dopamine antagonists. J Ocular Pharmacol 10: 371–377

    Google Scholar 

  • Daly SA, Waddington JL (1992) Two directions of dopamine D1/D2 receptor interaction in studies of behavioral regulation: a finding generic to four new, selective dopamine D1 receptor antagonists. Eur J Pharmacol 213: 251–258

    PubMed  Google Scholar 

  • Daniele E, Govoni S, Lograno MD (1990) Functional and binding studies on dopamine D-1 receptors in districts controlling intraocular pressure. Pharmacol Res 22 [Suppl 1]: 55–58

    Google Scholar 

  • Eisenlohr JE, Langham ME (1962) The relationship between pressure and volume changes in living and dead rabbit eyes. Invest Ophthalmol 1: 63–77

    PubMed  Google Scholar 

  • Elliott WJ, Karnezis TA, Silverman RA, Geanon J, Tripathi RC, Murphy B (1991) Intraocular pressure increases with fenoldopam, but not nitroprusside, in hypertensive humans. Clin Pharmacol Ther 49: 285–293

    PubMed  Google Scholar 

  • Elena PP, Denis P, Kosina-Boix M, Lapalus P (1989) Dopamine receptors in rabbit and rat eye: characterisation and localisation of DA1 and DA2 binding sites. Curr Eye Res 8: 75–83

    PubMed  Google Scholar 

  • Flammer J, Gasser P, Shaw S (1986) Intraokuläre Katecholaminkonzentrationen. Klin Monatsbl Augenheilkd 188: 503–504

    Google Scholar 

  • Fouriezos G, Hansson P, Wise RA (1978) Neuroleptic-induced attenuation of brain stimulation reward in rats. J Comp Physiol Psychol 92: 661–671

    PubMed  Google Scholar 

  • Green K, Elijah D (1979) Drug effects on aqueous humor formation and pseudo-facility in normal rabbit eyes. Exp Eye Res 33: 239–245

    Google Scholar 

  • Hariton C (1992) Biphasic dose-dependent effects of dopamine and involvement of dopamine autoreceptors on intra-ocular pressure in the rabbit. J Auton Pharmacol 12: 335–347

    PubMed  Google Scholar 

  • Hiromatsu S, Araie M, Fujimori K (1994) Endogenous catecholamine concentratios in rat iris-ciliary body. Jpn J Ophthalmol 38: 123–128

    PubMed  Google Scholar 

  • Kebabian JW, Calne DB (1979) Multiple receptors for dopamine. Nature 277: 93–96

    PubMed  Google Scholar 

  • Karnezis TA, Murphy MB (1988) Dopamine receptors and intraocular pressure. Trends Pharmacol Sci 9: 389–390

    PubMed  Google Scholar 

  • Karnezis TA, Murphy MB, Weber RR, Nelson K, Tripathi BJ, Tripathi R (1988) Effects of selective dopamine-1 receptor activation on intraocular pressure in man. Exp Eye Res 47: 689–697

    PubMed  Google Scholar 

  • Karnezis TA, Tripathi BJ, Dawson G, Murphy MB, Gupta P, Tripathi RC (1989) Effects of dopamine receptor activation on the level of cyclic AMP in the trabecular meshwork. Invest Ophthalmol Vis Sci 30: 1090–1094

    PubMed  Google Scholar 

  • Lograno MD, Daniele E, Govoni S (1990) Biochemical and functional evidence for the presence of dopamine D1 receptors in the bovine ciliary body. Exp Eye Res 51: 495–501

    PubMed  Google Scholar 

  • Lustig A (1983) Verstärkt Bromocriptin die Wirkung augeninnendrucksenkender Mittel? Dtsch Med Wochenschr 108: 1656–1657

    PubMed  Google Scholar 

  • Mancino R, Cerulli L, Amenta F (1992) Direct demonstration of D1-like receptor sites in the ciliary body of the rabbit eye by light microscope autoradiography. Naunyn Schmiedebergs Arch Pharmacol 346: 644–648

    PubMed  Google Scholar 

  • Markstein R, Gull P, Rüdeberg C, Urwyler S, Jaton AL, Kalkman HO, Dixon AK, Hoyer D (1996a) SDZ GLC-756, a novel octahydrobenzo[g]quinoline derivative, exerts opposing effects on dopamine D1 and D2 receptors. J Neural Transm 103: 17–30

    PubMed  Google Scholar 

  • Markstein R, Gull P, Rüderberg C, Urwyler S, Jaton AL, McAllister K, Dixon AK, Hoyer D (1996b) SDZ PSD-958, a novel D-1 receptor antagonist with limbic selectivity. J Neural Transm 103: 261–276

    PubMed  Google Scholar 

  • Masson G, Mestre D, Blin O (1993) Dopaminergic modulation of visual sensitivity in man. Fundam Clin Pharmacol 7: 449–463

    PubMed  Google Scholar 

  • McLeod RM, Lehmeyer JE (1974) Studies on he mechanism of the dopamine-mediated inhibition of prolactin secretion. Endocrinology 94: 1077–1084

    PubMed  Google Scholar 

  • Mekki QA, Turner P (1985) Stimulation of dopamine receptors (type 2) lowers human intraocular pressure. Br J Ophthalmol 69: 909–910

    PubMed  Google Scholar 

  • Mekki QA, Warrington SJ, Turner P (1984) Bromocriptin eyedrops lower intraocular pressure without affecting prolactine levels [letter]. Lancet 1: 287–288

    PubMed  Google Scholar 

  • Oroz JS, Domenech JS, Garcia MG, Martinez VP (1991) Effects of topical dihydroergocristine on intraocular pressure, aqueous humor dynamics and pupil diameter in conscious rabbits. A comparative study with timolol and pilocarpine. Med Find Exp Clin Pharmacol 13: 213–238

    Google Scholar 

  • Potter DE, Ogidigben MJ, Health AR (1993) Ocular actions of an octahydrobenzo[f]quinoline: Ha117. Eur J Pharmacol 236: 61–68

    PubMed  Google Scholar 

  • Prünte C, Flammer J (1995) The novel Dopamine D-1 antagonist and D-2 agonist, SDZ GLC-756, lowers IOP in normal human volunteers and glaucoma patients. Ophthalmology 102: 1291–1297

    PubMed  Google Scholar 

  • Rogawski MA (1987) New directions in neurotransmitter action: dopamine provides some important clues. Trends Neurosci 10: 200–205

    Google Scholar 

  • Setler PE, Sarau HM, Zirkle CL, Saunders HL (1978) The central effects of a novel dopamine agonist. Eur J Pharmacol 50: 419–430

    PubMed  Google Scholar 

  • Sibley DR, Monsma FJ Jr (1992) Molecular biology of dopamine receptors. Trends Pharmacol Sci 13: 61–69

    PubMed  Google Scholar 

  • Siegel MJ, Lee P-Y, Podos SM, Mittag TW (1987) Effect of topical pergolide on aqueous dynamics in normal and glaucomatous monkeys. Exp Eye Res 44: 227–233

    PubMed  Google Scholar 

  • Stone RA, Laties AM, Hemmings HC Jr, Quimet CC, Greengard P (1986) DARPP-32 in the ciliary epithelium of the eye: a neurotransmitter-regulated phosphoprotein of brain localizes to secretory cells. J Histochem Cytochem 34: 1465–1468

    PubMed  Google Scholar 

  • Stoof JC, Kebabian JW (1981) Opposing roles for D-1 and D-2 receptors in efflux of cyclic AMP from rat neostriatum. Nature 294: 366–368

    PubMed  Google Scholar 

  • Toris CB, Tafoya ME, Camras CB, Yablonski ME (1995) Effects of apraclonidine on aqueous humor dynamics in human eyes. Ophthalmology 102: 456–461

    PubMed  Google Scholar 

  • Tsuruta K, Frey EA, Grewe CW, Cote TE, Eskay RL, Kebabian JW (1981) Evidence that LY141865 specifically stimulates the D-2 receptor. Nature 292: 463–465

    PubMed  Google Scholar 

  • Winlow W, Markstein, R (1986) The neurobiology of dopamine systems. Manchester University Press, Manchester

    Google Scholar 

  • Wax MB (1993) Does dopamine act at dopamine receptors in the ciliary epithelia? Exp Eye Res 56Z: 371–373

    Google Scholar 

  • Yablonski ME, Zimmerman TJ, Waltman SR, Becker B (1978) A fluorometric study of the effect of topical timolol on aqueous humor dynamics. Exp Eye Res 27: 135–142

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. C. Prünte

    Present address: University Eye Clinic, Basel

Authors and Affiliations

  1. Preclinical Research, Sandoz Pharma Ltd., Basel, Switzerland

    I. Nuttli, R. Markstein & C. Kohler

Authors
  1. C. Prünte
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. Nuttli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Markstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Kohler
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Prünte, C., Nuttli, I., Markstein, R. et al. Effects of dopamine D-1 and D-2 receptors on intraocular pressure in conscious rabbits. J. Neural Transmission 104, 111–123 (1997). https://doi.org/10.1007/BF01273174

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01273174

Keywords

Search

Navigation