| Morphine tolerance increases [3H]MK-801 binding affinity and constitutive neuronal nitric oxide synthase expression in rat spinal cord. | |
MedLine Citation:
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PMID: 11064618 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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N-Methyl-D-aspartate (NMDA) receptor antagonists and nitric oxide synthase (NOS) inhibitors inhibit morphine tolerance. In the present study, a lumbar subarachnoid polyethylene (PE10) catheter was implanted for drug administration to study alterations in NMDA receptor activity and NOS protein expression in a morphine-tolerant rat spinal model. Antinociceptive tolerance was induced by intrathecal (i.t.) morphine infusion (10 micrograms h-1) for 5 days. Co-administered (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) (10 micrograms h-1 i.t.) with morphine was used to inhibit the development of morphine tolerance. Lumbar spinal cord segments were removed and prepared for [3H]MK-801 binding assays and NOS western blotting. The binding affinity of [3H]MK-801 was higher in spinal cords of morphine-tolerant rats (mean (SEM) KD = 0.41 (0.09) nM) than in control rats (1.50 (0.13) nM). There was no difference in Bmax. Western blot analysis showed that constitutive expression of neuronal NOS (nNOS) protein in the morphine-tolerant group was twice that in the control group. This up-regulation was partially prevented by MK-801. The results suggest that morphine tolerance affects NMDA receptor binding activity and increases nNOS expression in the rat spinal cord. |
Authors:
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C S Wong; M M Hsu; Y Y Chou; P L Tao; C S Tung |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of anaesthesia Volume: 85 ISSN: 0007-0912 ISO Abbreviation: Br J Anaesth Publication Date: 2000 Oct |
Date Detail:
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Created Date: 2000-11-09 Completed Date: 2000-11-09 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372541 Medline TA: Br J Anaesth Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 587-91 Citation Subset: IM |
Affiliation:
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Department of Anesthesiology, National Defense Medical Center, Taipei, Taiwan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analgesics, Opioid
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pharmacology* Animals Dizocilpine Maleate / pharmacology Drug Tolerance / physiology* Excitatory Amino Acid Antagonists / pharmacology Male Morphine / pharmacology* Nitric Oxide Synthase / metabolism* Nitric Oxide Synthase Type I Rats Rats, Sprague-Dawley Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors, metabolism* Spinal Cord / drug effects, metabolism Up-Regulation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Analgesics, Opioid; 0/Excitatory Amino Acid Antagonists; 0/Receptors, N-Methyl-D-Aspartate; 57-27-2/Morphine; 77086-22-7/Dizocilpine Maleate; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nos1 protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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