Inhibitory interaction of cannabinoid CB1 receptor and dopamine D2 receptor agonists on voltage-gated currents of goldfish cones

May 13, 2004Visual neuroscience

How Cannabis and Dopamine Signals Together Reduce Electrical Activity in Goldfish Light-Sensing Cells

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Abstract

At concentrations above 1 microM, the cannabinoid CB1 receptor agonist WIN 55212-2 decreases outward currents in goldfish retinal cones.

WIN 55212-2 exhibits biphasic effects on membrane currents, increasing them at low concentrations and decreasing them at high concentrations.
Dopamine D2 receptor agonist quinpirole at 50 microM suppresses outward currents by approximately 20%.
Quinpirole at concentrations below 10 microM completely blocks the enhancement of currents caused by low concentrations of WIN.
The action of quinpirole is mediated through a D2 receptor-Gi/o coupled mechanism, as indicated by the blockade from sulpiride and pertussis toxin.
The effects of high concentrations of WIN and quinpirole are nonadditive, suggesting they operate through the same signaling pathway to reduce membrane currents.

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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 microM) increased the currents via Gs, while higher concentrations (>1 microM) decreased the currents via Gi/Go. Neither dopamine nor the D2 agonist quinpirole (1-20 microM) had a significant effect on either Iout or ICa. Quinpirole at 50 microM had a mild suppressive (approximately 20%) effect on Iout. However, quinpirole (<10 microM) completely blocked the enhancement of both currents seen with 0.7 microM 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 microM quinpirole (approximately 20%) was not additive with the suppressive effect of 3 microM WIN (approximately 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).

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Inhibitory interaction of cannabinoid CB1 receptor and dopamine D2 receptor agonists on voltage-gated currents of goldfish cones

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