Modulation of dopamine release in the guinea-pig retina by G(i)- but not by G(s)- or G(q)-protein-coupled receptors

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 alpha(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 (ACTH1-24 and the beta-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 alpha(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.