| Objective: Dopamine is an important catecholamine neurotransmitter in the human central nervous system and an important feeding regulator.Dopamine plays an important role in regulating many functions such as cognition,emotion,hunger,satiety and exercise.The hypothalamic paraventricular nucleus(PVN)is an important brain nucleus involved in regulating food intake.The purpose of this study was to investigate the expression of dopamine D1 receptor in PVN,and to investigate the intracellular injection of dopamine D1 receptor agonist Fenoldopam mesylate or D1 receptor antagonist Rotundine to determine the regulation of rat PVN dopamine signaling pathway on feeding,gastric acid secretion and gastric motility.Methods: Fluorescence immunohistochemical staining and PCR were used to observe the expression of dopamine D1 receptor immunoreactive neurons and D1 receptor m RNA in PVN of rats.The effects of intravascular injection of D1 receptor agonist Fenoldopam mesylate or D1 receptor antagonist Rotundine on the feeding of rats were observed by means of brain nucleus tube placement technique,food intake measurement,Stomach movement record,gastric acid secretion measurement.The spontaneous activity of the rat is measured using a device such as a spontaneous activity measuring room and an animal foot scanner..Results: 1.Compared with rats injected with 1.2 ?g DA alone,microinjection of 0.12 ?g L-745870+1.2 ?g DA mixture and 3.6 ?g Rotundine+1.2 ?g DA mixture in PVN decreased the food intake of rats at 2 h(P<0.0-0.01),suggesting that DA can participate in the regulation of feeding through the D1 receptor and D4 receptor signaling pathway.However,the experimental results also found that the D1 receptor antagonist Rotundine inhibited DAinduced food intake significantly stronger than the D4 receptor antagonist L-745870(P<0.05),suggesting that the D1 receptor signaling pathway is dominant in regulating food intake;2.Fluorescence immunohistochemical staining showed that dopamine D1 receptor was observed in PVN of hypothalamus;The PCR results show that dopamine D1 receptor m RNA expression in PVN of the hypothalamus;3.PVN injection of different doses of D1 receptor agonist Fenoldopam mesylate(0.04 ?g,0.08 ?g,0.16 ?g,or 0.32 ?g),the gastric motility of the rats was significantly enhanced,the gastric acid secretion was significantly increased and the food intake was significantly increased.,and showed a dose-dependent relationship(P<0.05-0.01),and Fenoldopam mesylate promoted the feeding effect for more than 8 h;4.PVN injection of different doses of D1 receptor antagonist Rotundine(0.4 ?g,0.08 ?g,0.16 ?g,0.32 ?g)can inhibit gastric motility in rats,significantly reduce gastric acid secretion in rats,and the food intake of rats is significantly reduced.and also showed a dose-dependent relationship(P<0.05-0.01),and inhibition of food intake by 3.6 ?g Rotundine lasted for 4 h;5.PVN microinjection of Fenoldopam mesylate significantly increased gastric motility(P<0.05),increased gastric acid secretion(P<0.05),and increased food intake(P<0.05).PVN injection of Fenoldopam mesylate+Rotundine mixture,Fenoldopam mesylate induction The gastric promotion(P<0.05),gastric acid secretion(P<0.05)and food-feeding effect(P<0.05)decreased significantly;6.The D1 receptor antagonist Rotundine(3.6 ?g)and the receptor agonist Fenoldopam mesylate(0.16 ?g)did not affect spontaneous activity in rats compared with saline(P>0.05);Conclusion: Activation of dopamine D1 and D4 receptor signaling pathways in PVN can increase food intake and promote gastric gas and gastric acid secretion in rats.PVN dopaminergic neurons play an important role in feeding,gastric acid secretion and regulation of gastric motility. |
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