MrgC receptor activation reverses chronic morphine-evoked alterations of glutamate transporters and nNOS in rats.
- Author:
Hao HUANG
1
;
Qi LI
;
Yan-Guo HONG
;
Dong-Mei WANG
Author Information
1. Provincial Key Laboratory of Developmental and Neurological Biology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China. dmwang@fjnu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Amino Acid Transport System X-AG;
metabolism;
Animals;
Drug Tolerance;
Ganglia, Spinal;
metabolism;
Glutamates;
Morphine;
pharmacology;
Nitric Oxide Synthase Type I;
metabolism;
Pain;
Pain Measurement;
Peptide Fragments;
pharmacology;
Rats;
Rats, Sprague-Dawley;
Receptors, G-Protein-Coupled;
metabolism;
Spinal Cord;
metabolism
- From:
Acta Physiologica Sinica
2014;66(4):449-456
- CountryChina
- Language:Chinese
-
Abstract:
This study was aimed to investigate the mechanisms underlying the modulation effect of Mas-related gene (Mrg) C receptors (MrgC) on morphine tolerance. Saline, morphine (20 μg), morphine plus bovine adrenal medulla 8-22 (BAM8-22, 1 nmol) or (Tyr(6))-2-MSH-6-12 (MSH, 5 nmol) were administered intrathecally in rats for 6 days. Pain-related molecules in the spinal cord and dorsal root ganglion (DRG) were examined using Western blot, immunocytochemistry and RT-PCR techniques. The results showed that intrathecal administration of the selective MrgC receptor agonists (BAM8-22 or MSH) remarkably attenuated or abolished chronic morphine-evoked reduction in glutamate transporters (GLAST, GLT-1 and EAAC1) in the spinal cord and increase in neuronal nitric oxide synthase (nNOS) in the spinal cord as well as DRG. In addition, MrgC receptor-like immunoreactivity (IR) was detected in superficial laminae of the spinal cord. Chronic morphine induced significant increases in MrgC receptor-IR in the spinal cord and MrgC receptor mRNA levels in DRG. These results suggest that the modulation of pro-nociceptive mediators in the spinal cord and DRG underlies the inhibition of morphine tolerance by MrgC receptor activation.
