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S. Fan, S. Yazulla; Interaction of Cannabinoid CB1 Receptor and Dopamine D2 Receptor Agonists on Voltage-gated Currents of Goldfish Cones . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4167.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Dopamine is a light adaptive signal that desensitizes the retina while cannabinoids have been reported to increase photosensitivity. The presynaptic membrane of retinal goldfish cones has both dopamine D2- and cannabinoid CB1 receptors. This work focused on whether dopamine and cannabinoid receptor agonists interact to modulate voltage-dependent membrane currents of cones. Methods: The D2 receptor agonist quinpirole was dissolved in saline and stock solutions of cannabinoid CB1 receptor agonist WIN 55212-2 was prepared with DMSO. A conventional path-clamp method was used to record whole-cell currents from the inner segment of cones in goldfish retinal slices. Results focused on depolarization-evoked outward currents that largely represent the potassium current, IK(V). Results: WIN 55212-2 has biphasic actions: low concentrations (<1 µM) of WIN 55212-2 increased the outward currents via action on Gs, while higher concentrations (>1 µM) decreased the currents via action on Gi/Go. Low concentrations (<10 µM) of quinpirole alone had no consistent effects on the outward currents. When applied together with either low or high concentrations of WIN 55212-2, 10 µM quinpirole had no obvious effect; the usual biphasic effect of WIN was still observed. However, 50 µM quinpirole consistently decreased the outward currents when applied alone. The suppressive action of 50 µM quinpirole masked the enhancing effect of low concentrations of WIN but was not additive to the suppressive effect of high concentrations of WIN. The maximal suppression of 50% with either compound was not increased by the combination. Conclusion: D2 and CB1 agonists modulate cone membrane currents, suggesting a cooperative role in shaping the cone light response. The non-additive effect of high concentrations of WIN 55212-2 and quinpirole suggests that both decrease the outward current via the same transduction pathway, Gi/Go-protein kinase A.
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