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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 354, Issue 6, pp 791–795 | Cite as

Cannabinoid receptor-mediated inhibition of dopamine release in the retina

  • Eberhard Schlicker
  • Jörg Timm
  • Manfred Göthert
Short Communication

Abstract

The possible occurrence of cannabinoid (CB) receptors was studied on superfused guinea-pig retinal discs preincubated with [3H]dopamine or [3H]noradrenaline. Tritium overflow was evoked either electrically (3 Hz) or by re-introduction of Ca2+, 1.3 mM after superfusion with Ca2+-free medium containing K+ 30 rnM. The accumulation of [3H]dopamine ([3H]DA) and [3H]noradrenaline ([3H]NA) was inhibited by the selective inhibitor of the neuronal dopamine transporter GBR-12909 (pIC50% 7.29 and 7.41, respectively) but not by the selective inhibitor of the neuronal noradrenaline transporter desipramine (1 μM). The electrically or Ca2+-evoked tritium overflow in retinal discs preincubated with [3H]DA or [3H]NA was reduced by the CB receptor agonists CP-55,940 and WIN 55,212-2 (pIC50% in discs preincubated with [3H]NA, electrical stimulation: 7.03 and 6.70, respectively) but not affected by the inactive S(−)enantiomer of the latter, WIN 55,212-3 (up to 10 μM). The concentration-response curve of WIN 55,212-2 was shifted to the right by the CB1 receptor antagonist SR 141716 (apparent pA2: 8.29) which, by itself, increased the evoked overflow. The facilitatory effect of SR 141716 was not affected by GBR-12909 and the dopamine receptor antagonist haloperidol. In conclusion, the dopaminergic neurones of the guinea-pig retina can be labelled by both [3H]DA and [3H]NA. Transmitter release from the dopaminergic neurones is inhibited by activation of cannabinoid receptors of the CB1 type, which appear to be tonically activated by an endogenous CB receptor ligand.

Key words

Cannabinoid receptors Dopamine release WIN 55,212-2 CP-55,940 SR 141716 Superfusion experiments Guinea-pig retina 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Eberhard Schlicker
    • 1
  • Jörg Timm
    • 1
  • Manfred Göthert
    • 1
  1. 1.Institut fur Pharmakologie und ToxikologieRheinische Friedrich-Wilhelms-Universität BonnBonnGermany

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