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Modulation of dopamine release in the guinea‐pig retina by G i ‐ but not by G s ‐ or G q ‐protein‐coupled receptors
Author(s) -
Weber Bernd,
Schlicker Eberhard
Publication year - 2001
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1046/j.1472-8206.2001.00056.x
Subject(s) - oxotremorine , endocrinology , medicine , agonist , dopamine , chemistry , melatonin , antagonist , muscarinic acetylcholine receptor , biology , receptor
The modulation of dopamine release from the guinea‐pig retina was studied using maximally effective concentrations of 10 agonists acting on G i ‐, G s ‐ or G q ‐protein‐coupled receptors (PCRs). Retinal discs were preincubated with [ 3 H]noradrenaline and superfused; tritium overflow was evoked electrically. The following compounds acting on G i ‐PCRs reduced the tritium overflow, which represents quasi‐physiological dopamine release under the experimental conditions of our study: the dopamine and α 2 ‐adrenoceptor agonist B‐HT 920 by 95%, the muscarinic agonist oxotremorine by 96%, melatonin by 94%, the cannabinoid agonist WIN 55,212–2 by 71% and histamine by 66%. Tritium overflow was not affected by serotonin or by agonists acting on G s ‐PCRs (ACTH 1‐24 and the β‐adrenoceptor agonist procaterol) and G q ‐PCRs (angiotensin II and bradykinin). The effects of B‐HT 920, oxotremorine and melatonin were studied in more detail using appropriate antagonists. The inhibitory effect of a submaximally active concentration of B‐HT 920 was counteracted by the dopamine D 2/3 antagonist haloperidol but not affected by the α 2 ‐adrenoceptor antagonist phentolamine. The muscarinic antagonist atropine shifted to the right the concentration‐response curve of oxotremorine (pA 2 8.7) and the melatonin MT 2 antagonist 4‐P‐PDOT produced a rightward shift of the concentration‐response curve of melatonin (pA 2 10.6). Melatonin was also studied in superfused brain slices (from the guinea‐pig) preincubated with [ 3 H]noradrenaline. The electrically evoked tritium overflow in cerebrocortical, hippocampal and hypothalamic slices (representing quasi‐physiological noradrenaline release) and in striatal slices (representing quasi‐physiological dopamine release) was not affected by melatonin at a concentration that causes the maximum effect in retinal discs. In conclusion, dopamine release in the guinea‐pig retina is inhibited via G i ‐PCRs including dopamine (D 2/3 ), muscarinic and melatonin (MT 2 ) receptors but not affected via any of the G s ‐ or G q ‐PCRs under study. Unlike in the retina, melatonin fails to inhibit monoamine release in four brain regions of the guinea‐pig.