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


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.


RESULTS
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 (10mg/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.


CONCLUSIONS
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.
Yoshikawa
Takashi
T
Strategic Planning & Business Development Division, Dainippon Sumitomo Pharma. Co., Ltd. Osaka, Japan.
Yoshida
Naoyuki
N
D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology; D005746:Gastric Emptying; D008297:Male; D010078:Oxazines / Q000008:administration & dosage / Q000494:pharmacology; D019257:Quinpirole / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000187:drug effects / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000494:pharmacology
D001578:Benzopyrans; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D005663:Furans; D010078:Oxazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; C090812:7-(N,N-dipropylamino)-5,6,7,8-tetrahydronaphtho(2,3-b)dihydro-2,3-furan; D019257:Quinpirole; D015081:2-Naphthylamine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin