The possible involvement of dopamine D3 receptors in the regulation of gastric emptying in rats

Aim: The inhibitory effect of dopamine on gastric motility is thought to be mediated via a decrease in acetylcholine release resulting from stimulation of enteric neuronal dopamine D-2 receptors. The aim of this study was to investigate the possible involvement of the dopamine D-3 receptor in the regulation of gastric motility in rats using selective dopamine D-3 receptor agonists or a dopamine D-3 receptor antagonist. Main methods: Gastric emptying was assessed using the phenol red method after rats were treated with varying doses of dopamine D-3 receptor agonists or a dopamine D-3 receptor antagonist. Key findings: S(+)-PD 128,907 (0.01-1 mg/kg. s.c.), a selective dopamine D-3 receptor agonist, dose-dependently delayed gastric emptying in rats. Other dopamine D-3 receptor agonists (i.e., R(+)-7-OH-DPAT [0.03-1 mg/kg, s.c.] and quinpirole [0.01-1 mg/kg, s.c.]) also delayed gastric emptying in rats. Both the selective dopamine D-1 and D-5 receptor agonist SKF-38393 and the selective dopamine D-4 receptor agonist PD 168,077 failed to delay gastric emptying in rats. The selective dopamine D-3 receptor antagonist (+)-S 14297 (10 mg/kg, s.c.) partially inhibited the S(+)-PD 128,907-induced delay in gastric emptying. Although an administration of S(+)-PD 128,907 (1-100 mu g/kg) into the 4th cerebral ventricle partially and dose-dependently delayed gastric emptying in rats, its administration into the lateral cerebral ventricle did not affect gastric emptying. Significance: The results presented here suggest that peripheral dopamine D-2 receptors and, at least in part, dopamine D-3 and central dopamine D-2/D-3 receptors play an important role in the regulation of gastric motility in rats. (C) 2010 Elsevier Inc. All rights reserved.