Modulation of [³H]dopamine release from rabbit retina

The calcium-dependent release of [³H]dopamine ([³H]DA) elicited by field stimulation or potassium is modulated through activation of stereoselective inhibitory DA autoreceptors of the D-2 subtype that are pharmacologically different from the D-1 DA receptor subtype linked to the stimulation of adenylate cyclase (EC 4.6.1.1). The D-2 DA autoreceptors appear to be endogenously activated by DA because DA receptor antagonists such as S-sulpiride increased the stimulation-evoked release of [³H]DA. Nanomolar concentrations of norepinephrine (NE) and epinephrine (E) inhibited in a concentration-dependent manner the electrical stimulation-evoked release of [³H]DA. The inhibitory effect of these catecholamines was not modified by S-sulpiride, which, on the contrary, selectively antagonized the inhibition of [³H]DA release elicited by exogenous DA. Phentolamine or (±)-propranolol did not affect the release of [³H]DA from rabbit retina. The α antagonist phentolamine competitively antagonized the inhibitory effect of both NE and E, which suggests that these catecholamines activate α receptors in retina. The decrease by catecholamines of the calcium-dependent release of [³H]DA appears not to involve β adrenoceptors because their inhibitory effect was not modified by propranolol. Under identical experimental conditions (i.e., nomifensine, 30 μM), serotonin did not modify the stimulated release of [³H]DA. In conclusion, in the rabbit retina, DA autoreceptors of the D-2 subtype appear to modulate endogenously released DA whereas inhibitory presynaptic α receptors might be of pharmacological importance as sites of action for retinal or blood-borne catecholamines.