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

AimThe 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 D2 receptors. The aim of this study was to investigate the possible involvement of the dopamine D3 receptor in the regulation of gastric motility in rats using selective dopamine D3 receptor agonists or a dopamine D3 receptor antagonist.Main methodsGastric emptying was assessed using the phenol red method after rats were treated with varying doses of dopamine D3 receptor agonists or a dopamine D3 receptor antagonist.Key findingsS(+)-PD 128,907 (0.01–1 mg/kg, s.c.), a selective dopamine D3 receptor agonist, dose-dependently delayed gastric emptying in rats. Other dopamine D3 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 D1 and D5 receptor agonist SKF-38393 and the selective dopamine D4 receptor agonist PD 168,077 failed to delay gastric emptying in rats. The selective dopamine D3 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 μg/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.SignificanceThe results presented here suggest that peripheral dopamine D2 receptors and, at least in part, dopamine D3 and central dopamine D2/D3 receptors play an important role in the regulation of gastric motility in rats.