Dopamine is a light-adaptive signal that desensitizes the retina,
while cannabinoids reportedly increase photosensitivity. The
presynaptic membrane of goldfish retinal cones has dopamine D2
receptors and cannabinoid CB1 receptors. This work focused on whether
dopamine D2 receptor agonist quinpirole and cannabinoid CB1 receptor
agonist WIN 55212-2 (WIN) interacted to modulate voltage-dependent
membrane currents of cones. A conventional patch-clamp method was used
to record depolarization evoked whole-cell outward currents
(Iout) and an inward calcium current
(ICa) from the inner segment of cones in goldfish
retinal slices. WIN had biphasic actions: low concentrations (<1
μM) increased the currents via Gs, while higher
concentrations (>1 μM) decreased the currents via
Gi/Go. Neither dopamine nor the D2 agonist quinpirole (1–20
μM) had a significant effect on either Iout or
ICa. Quinpirole at 50 μM had a mild suppressive
(∼20%) effect on Iout. However, quinpirole
(<10 μM) completely blocked the enhancement of both currents
seen with 0.7 μM WIN. The effect of quinpirole was blocked by
sulpiride and by pertussis toxin, indicating that quinpirole was acting
via a D2 receptor-Gi/o coupled mechanism. The suppressive
action of 50 μM quinpirole (∼20%) was not additive with the
suppressive effect of 3 μM WIN (∼40%). D2 agonists via
Gi/o oppose the action of low concentrations of CB1 agonists acting
via Gs to modulate cone membrane currents, suggesting a role
in shaping the cone light response and/or sensitivity to changes in
ambient light conditions. The nonadditive effect of high concentrations
of WIN and quinpirole suggests that both decrease membrane currents
via the same transduction pathway, Gi/Go protein kinase A
(PKA).