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 beta-adrenoceptors (beta-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 beta-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 beta-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 beta(1)-AR or beta(2)-AR did not affect the inhibition of strip contraction by NE in control rats, but beta(1)-AR blockage obviously enhanced the half maximal inhibitory concentration value of NE in 6-OHDA rats. Selective inhibition of beta(3)-AR blocked the effect of NE significantly in both control and 6-OHDA rats. The protein expression of beta(1)-AR, but not beta(2)-AR and beta(3)-AR in gastric muscularis externa was increased significantly in 6-OHDA rats. In conclusion, beta(3)-AR involves the regulation of gastric motility in control rats, whereas the upregulation of beta(1)-AR is responsible for enhanced NE reactivity in 6-0HDA rats and therefore is involved in the formation of gastroparesis. The effect of both beta(1)-AR and beta(3)-AR on gastric motility is independent of the enteric nervous system.