Effect of Tianqi antitremor granules on behavioral manifestations and expression of G protein-coupled receptor kinase 6 and β-arrestin1 in levodopa-induced dyskinesia in a rat model of Parkinson's disease.

Abstract

BACKGROUND:

Recent studies have shown that expression of G protein-coupled receptor kinase 6 (GRK6) and β-arrestin1 in the striatum is closely associated with hyperactive dopamine receptors in rats with levodopa-induced dyskinesia (LID). Our research group has shown that Tianqi antitremor granules have a significant effect on the motor complications of Parkinson's disease (PD). However, whether Tianqi antitremor granules have an effect on the behavioral manifestations and expression of GRK6 and β-arrestin1 in rats with LID is unknown.

METHODS:

Rats with PD received twice daily intraperitoneal injections of levodopa for 4 weeks to induce dyskinesia. Rats with LID were randomly divided into five groups: an LID-control group, an LID group, a levodopa plus Tianqi antitremor granules as traditional Chinese medicine (TCM)-low group, a levodopa plus TCM-medium group, and levodopa plus TCM-high group. Peak intensity of rotations was measured. GRK6 and β-arrestin1 expression in the striatum of the dyskinetic rats was observed by immunohistochemistry and Western blotting.

RESULTS:

Pulsatile treatment with levodopa induced abnormal involuntary movements in rats with PD similar to LID in patients with PD. We found that repeated levodopa administration increased peak rotations in dyskinetic rats. However, peak rotations were decreased in rats given levodopa plus the different doses of Tianqi antitremor granules. In accordance with changed behavior, GRK6 and β-arrestin1 expression was decreased in rats with PD and was persistently low in rats with LID, but this decrease was prevented by coadministration of levodopa and Tianqi antitremor granules.

CONCLUSION:

Tianqi antitremor granules ameliorated levodopa-induced dyskinetic behavior, reversed the decrease in GRK6 and β-arrestin1 expression, and acted as a useful adjunctive medicine for the treatment of LID.

• Authors: Na Wu, Xinxin Yang, Lu Song, Jianglei Wei, Zhenguo Liu
• Journal: Drug design, development and therapy (Drug Des Devel Ther) Vol. 7 Pg. 1481-9 ( 2013) ISSN: 1177-8881 [Electronic] New Zealand
• PMID: 24376341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiparkinson Agents
• Arrestins
• Drugs, Chinese Herbal
• beta-Arrestins
• Levodopa
• G-Protein-Coupled Receptor Kinases
• G-protein-coupled receptor kinase 6

Topics

• Animals
• Antiparkinson Agents (administration & dosage, pharmacology)
• Arrestins (genetics)
• Behavior, Animal (drug effects)
• Blotting, Western
• Corpus Striatum (drug effects, metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (administration & dosage, pharmacology)
• Dyskinesia, Drug-Induced (drug therapy, physiopathology)
• Female
• G-Protein-Coupled Receptor Kinases (genetics)
• Immunohistochemistry
• Levodopa (toxicity)
• Parkinsonian Disorders (drug therapy, physiopathology)
• Rats
• Rats, Sprague-Dawley
• beta-Arrestins