[The roles of dopamine 4 receptor in MPTP-induced gastrointestinal mucosal injury in rats].
OBJECTIVE
Using the dopamine 4 receptor (D(4)) agonist quinpirole (Q.) and antagonist clozapine (C.) to investigate the role of D(4) in MPTP induced gastrointestinal injury in rat.


METHODS
SD rats were randomly divided into 8 groups (n = 5 approximately 9 each group): NS as control; Q. 0.5 mg/kg; Q. 1 mg/kg; C. 10 mg/kg; Q. 0.5 mg/kg + MPTP; Q. 1 mg/kg + MPTP; and MPTP l mg/100 g. After treated with the different chemicals, the gastric and duodenal mucosa lesion index (LI) was recorded. Gastric and duodenal mucosa was collected to assay NO and iNOS by spectrophotometer.


RESULTS
(1) MPTP peritoneal injection induced significant gastro-duodenal mucosa injury; both gastric and duodenal LI were 5 approximately 6-fold higher than control group (P < 0.01). (2) Q. or C. used alone showed no effect on gastro-duodenal mucosa, Q. used before MPTP could resist the MPTP-induced mucosa injury, especially in duodenum (P < 0.01). This effectiveness is dose dependent. C. had no effect on gastro-duodenal mucosa protection. (3) The mucosal NO concentration and iNOS activity in MPTP group were lower than that in control, especially in duodenum (P < 0.05). They were negative correlated with LI.


CONCLUSIONS
MPTP peritoneal injection induced significant gastro-duodenal mucosa injury in rat, mediated partially by decreasing the activity of mucosa iNOS and NO concentration. D(4) agonist Q. could resist the effectiveness of MPTP-induced mucosa injury, while the antagonist C. had no effect.
Zhou
Jun
J
Department of Gastroenterology, Third Hospital of Peking University, Beijing 100083, China.
Duan
Li-ping
LP
Yang
Xue-ling
XL
Dong
Xiu-yun
XY
Lin
San-ren
SR
D000818:Animals; D003024:Clozapine / Q000494:pharmacology; D019610:Cytoprotection; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D007413:Intestinal Mucosa / Q000473:pathology*; D020267:MPTP Poisoning / Q000473:pathology*; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D050638:Receptors, Dopamine D4
C493601:Drd4 protein, rat; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D019257:Quinpirole; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D003024:Clozapine