Upregulation of β1-adrenoceptors is involved in the formation of gastric dysmotility in the 6-hydroxydopamine rat model of Parkinson's disease.
Gastrointestinal dysmotility is one of the nonmotor symptoms of Parkinson's disease (PD). Gastroparesis and upregulated β-adrenoceptors (β-ARs) have been reported in rats with bilateral microinjection of 6-hydroxydopamine (6-OHDA) in the substantia nigra, but the underlying mechanism is unclear. The aim of the current study is to investigate the role of β-ARs in gastroparesis in 6-OHDA rats. Gastric motility was studied through strain gauge measurement. Immunofluorescence, real-time reverse transcription-polymerase chain reaction and Western blotting were performed to examine the expression of β-ARs. Norepinephrine (NE) inhibited gastric motility in a dose-dependent fashion in both control and 6-OHDA rats, but much stronger adrenergic reactivity was observed in the 6-OHDA rats. The inhibition of gastric motility by NE in both control and 6-OHDA rats was not affected by tetrodotoxin, a neural sodium channel blocker. Blocking β1-AR or β2-AR did not affect the inhibition of strip contraction by NE in control rats, but β1-AR blockage obviously enhanced the half maximal inhibitory concentration value of NE in 6-OHDA rats. Selective inhibition of β3-AR blocked the effect of NE significantly in both control and 6-OHDA rats. The protein expression of β1-AR, but not β2-AR and β3-AR in gastric muscularis externa was increased significantly in 6-OHDA rats. In conclusion, β3-AR involves the regulation of gastric motility in control rats, whereas the upregulation of β1-AR is responsible for enhanced NE reactivity in 6-OHDA rats and therefore is involved in the formation of gastroparesis. The effect of both β1-AR and β3-AR on gastric motility is independent of the enteric nervous system.
Gastrointestinal Research Group, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Jin
J
Song
Gastrointestinal Research Group, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Lifei
L
Zheng
Gastrointestinal Research Group, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Xiaoli
X
Zhang
Gastrointestinal Research Group, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Xiaoyan
X
Feng
Gastrointestinal Research Group, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Ruifang
R
Fan
Gastrointestinal Research Group, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Lu
L
Sun
Gastrointestinal Research Group, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Feng
F
Hong
Gastrointestinal Research Group, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Yue
Y
Zhang
Gastrointestinal Research Group, Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China. Electronic address: zhu_jx@ccmu.edu.cn.
Jinxia
J
Zhu
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000502:physiology*; D018589:Gastroparesis / Q000209:etiology*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D016627:Oxidopamine / Q000378:metabolism*; D010300:Parkinson Disease / Q000150:complications / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects; D015854:Up-Regulation
D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D016627:Oxidopamine; D009638:Norepinephrine