Pharmacological and functional characterisation of dopamine D4 receptors in the rat retina.

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Patel S, Chapman KL, Marston D, Hutson PH, Ragan CI

Pharmacological and functional characterisation of dopamine D4 receptors in the rat retina.

Neuropharmacology. 2003 Jun;44(8):1038-46.

PubMed ID

12763097 [ View in PubMed

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Abstract

In the retina, activation of dopamine receptors, particularly the D2-like family (D2, D3, D4 receptor subtypes), with quinpirole suppresses the light sensitive cAMP pool and inhibits melatonin synthesis in photoreceptor cells. We have characterised rat retinal D4 receptors using the D4 selective radioligand [(125)I] L-750667 which bound specifically and saturably to rat retinal membranes with high affinity (K(d) 0.06+/-0.02 nM) and exhibited a D4 receptor pharmacology. Comparison of the binding kinetics of [(125)I] L-750667 and [(3)H] spiperone revealed B(max) values of 134+/-27 fmol/mg and 219+/-47 fmol/mg respectively, indicating that the dopamine D4 receptor is a major component of D2-like dopamine receptors in the rat retina. Modulation of retinal cAMP levels by quinpirole was used to evaluate the functional relevance of rat retinal dopamine D4 receptors. Quinpirole (0.03-3 micro ) produced a dose-related decrease of the light sensitive cAMP pool which was reversed by haloperidol, clozapine and the D4 selective antagonist, L-745870 with a rank order of potency suggesting that the quinpirole effect is due to activation of the dopamine D4 receptors. The D2 selective ligand L-741626 had no effect on the quinpirole response confirming that the D4 receptor is the major receptor subtype mediating dopamine induced suppression of adenylate cyclase in the retina.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Clozapine	Dopamine D4 receptor	Protein	Humans	Unknown	Antagonist	Details