Alpha-2 adrenoceptors modulate [³H]dopamine release from rabbit retina

In the rabbit retina, preloaded in vitro with [³H]dopamine, calcium-dependent release of radioactivity was elicited by a 1-min period of field stimulation of 3 Hz (20 mA, 2 msec). In the presence of the catecholamine uptake inhibitor nomifensine (30 μM), unlabeled catecholamines (0.01-3 μM), namely, dopamine, norepinephrine and epinephrine, inhibited in a concentration-dependent manner and field stimulation-evoked release of [³H]dopamine from the retina. The concentrations of dopamine, norepinephrine or epinephrine which inhibited by 50% the release of [³H]dopamine (IC₅₀) were 0.30, 0.25 μM, respectively. In the presence of 30 μM nomifensine, S-sulpiride (1 μM) significantly increased the calcium-dependent release of [³H]dopamine, suggesting that this dopamine antagonist blocks a receptor tonically activated by endogenous dopamine in the rabbit retina. In contrast, the alpha receptor antagonist phentolamine (1 μM) alone did not effect the release of [³H]dopamine from the retina. The inhibitory effect of norepinephrine and epinephrine on [³H]dopamine overflow was not modified by S-sulpiride which, on the contrary, selectively antagonized the effect of exogenous dopamine. Phentolamine (1 μM) competitively antagonized the inhibitory effect of norepinephrine and epinephrine on [³H]dopamine release, suggesting that these catecholamines activate alpha adrenoceptors in retina. In the absence of nomifensine, the selective alpha-2 agonist clonidine (IC₅₀ = 0.056 μM) inhibited the stimulation-evoked release of [³H]dopamine from retina, whereas the alpha agonist methoxamine was without effect. The inhibitory effect of clonidine was antagonized by yohimbine (1 μM), but not prazosin, suggesting that the release modulating alpha receptors of the retina are of the alpha-2 subtype. It is concluded that, in the rabbit retina, activation of alpha-2 adrenoceptors, which are distinct from the dopamine D-2 autoreceptors, inhibit the calcium-dependent release of [³H]dopamine. These retinal alpha-2 adrenoceptors might be of pharmacological importance as sites of action for catecholamines and therapeutic agents.