When it comes to opiates, just say NO Journal Article
| Author: | Pasternak, G. W. |
| Article Title: | When it comes to opiates, just say NO |
| Abstract: | Repeated use of opiate analgesic drugs such as morphine for the relief of chronic pain may result in the development of opiate tolerance and dependence, leading to a narrowing of the drug's therapeutic index and increased side effects. Previous preclinical work has shown that interruption of a signaling cascade involving the N-methyl-D-aspartate receptor and NO prevents morphine tolerance. In this issue of the JCI, Muscoli and colleagues extend our understanding of the role of NO in tolerance by demonstrating that, in mice, tolerance to chronic morphine administration is associated with NO conversion to peroxynitrite, which accumulates and nitrates tyrosine moieties within various proteins in the spinal cord (see the related article beginning on page 3530). This and other data suggest that peroxynitrite plays a role in opiate tolerance and that regulation of peroxynitrite may be utilized for the management of opiate-induced tolerance. |
| Keywords: | signal transduction; constipation; review; nonhuman; side effect; animals; mice; sedation; drug effect; tyrosine; confusion; drug mechanism; chronic pain; morphine; respiration depression; analgesics, opioid; glutamate receptor; superoxide dismutase; guanine nucleotide binding protein; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; analgesia; drug tolerance; protein derivative; opiate receptor; opiate addiction; adenylate cyclase; delta opiate receptor; glycoprotein p; n methyl dextro aspartic acid receptor; nitric oxide; receptors, n-methyl-d-aspartate; enkephalin; nociceptin; opiate derivative; neurotransmitter; peroxynitrite; 3 nitrotyrosine; cholecystokinin; glutamate ammonia ligase; guanylate cyclase; neuropeptide ff; rgs protein; vesicular glutamate transporter 1; peroxynitrous acid |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 117 |
| Issue: | 11 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 2007-11-01 |
| Start Page: | 3185 |
| End Page: | 3187 |
| Language: | English |
| DOI: | 10.1172/jci34035 |
| PUBMED: | 17975665 |
| PROVIDER: | scopus |
| PMCID: | PMC2045628 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 13" - "Export Date: 17 November 2011" - "CODEN: JCINA" - "Source: Scopus" |
