title: [MrgC receptor activation reverses chronic morphine-evoked alterations of glutamate transporters and nNOS in rats].
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.
authors.affiliation: Provincial Key Laboratory of Developmental and Neurological Biology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China. dmwang@fjnu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Huang
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Yan-Guo
authors.initials: YG
authors.lastname: Hong
authors.forename: Dong-Mei
authors.initials: DM
authors.lastname: Wang
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D000818:Animals; D004361:Drug Tolerance; D005727:Ganglia, Spinal / Q000378:metabolism; D005971:Glutamates; D009020:Morphine / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D010146:Pain; D010147:Pain Measurement; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D027322:Amino Acid Transport System X-AG; D005971:Glutamates; C000591603:Mrgprc protein, rat; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; C571042:bovine adrenal medulla 8-22; D009020:Morphine; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat