Modulation of [3H]-dopamine released by different frequencies of stimulation from rabbit retina

Abstract

Rabbit retinal pieces were incubated with [3H]-dopamine and superfused with Krebs solution. Calcium-dependent tritium release was elicited twice within each experiment by electrical field stimulation (360 pulses, 2 ms, 20 mA) at frequencies of 1 Hz, 3 Hz, and 6 Hz. The evoked release of [3H]-dopamine for the first period of stimulation (S1) was 2.09 +/- 0.23% (n = 5) at 1 Hz and was of similar magnitude at all other frequencies of stimulation employed. The D2-dopamine receptor agonist, LY 171555 (quinpirole HCl; 0.01-1 microM) added to the superfusion medium before the second period of stimulation, inhibited the calcium-dependent release of [3H]-dopamine in a concentration-dependent manner, and was more potent the lower the stimulation frequency. The isomer of quinpirole, LY 181990 (0.01-1 microM) did not inhibit the stimulation-evoked overflow of tritium, regardless of concentration or stimulation frequency. The stereoisomers of the D2-dopamine receptor antagonist sulpiride (0.01-3 microM) increased the calcium-dependent release of [3H]-dopamine in a concentration-dependent manner, being more potent the higher the frequency of stimulation. S-sulpiride was more potent than R-sulpiride at all stimulation frequencies. The inhibitory effect of quinpirole was stereoselectively antagonized by sulpiride, but not by LY 181990. The alpha-adrenoceptor antagonist phentolamine (1 microM) did not modify the quinpirole-induced inhibition of [3H]-dopamine release. When the synaptic concentration of dopamine was increased by the presence of the dopamine uptake inhibitor nomifensine (3 microM), the potency of the agonist quinpirole in inhibiting the release of [3H]-dopamine elicited by field stimulation at 1 Hz (180 pulses) was decreased. In contrast, the potency of S-sulpiride in enhancing the evoked release of [3H]-dopamine was increased when nomifensine was present in the superfusion medium. Picomolar concentrations of the hormone melatonin (0.1-10 nM) inhibited the calcium-dependent release of [3H]-dopamine from rabbit retina with the same potency regardless of the frequency of stimulation applied (1 Hz, 3 Hz or 6 Hz). The potency of D2-dopamine receptor agonists and antagonists in modifying [3H]-dopamine release from rabbit retina appears to depend on the synaptic concentration of dopamine which is altered by the frequency of stimulation, and by the dopamine uptake inhibitor nomifensine.(ABSTRACT TRUNCATED AT 400 WORDS)