QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Song, B. Articles by Marvizón, J. C. G. Search for Related Content PubMed PubMed Citation Articles by Song, B. Articles by Marvizón, J. C. G.

 Previous Article  |  Next Article 

The Journal of Neuroscience, March 1, 2003, 23(5):1847

Peptidases Prevent µ-Opioid Receptor Internalization in Dorsal Horn Neurons by Endogenously Released Opioids

Bingbing Song and Juan Carlos G. Marvizón

Center for Neurovisceral Sciences and Women's Health, Division of Digestive Diseases, Department of Medicine, Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095

To evaluate the effect of peptidases on µ-opioid receptor (MOR) activation by endogenous opioids, we measured MOR-1 internalization in rat spinal cord slices. A mixture of inhibitors of aminopeptidases (amastatin), dipeptidyl carboxypeptidase (captopril), and neutral endopeptidase (phosphoramidon) dramatically increased the potencies of Leu-enkephalin and dynorphin A to produce MOR-1 internalization, and also enhanced the effects of Met-enkephalin and -neoendorphin, but not endomorphins or -endorphin. The omission of any one inhibitor abolished Leu-enkephalin-induced internalization, indicating that all three peptidases degraded enkephalins. Amastatin preserved dynorphin A-induced internalization, and phosphoramidon, but not captopril, increased this effect, indicating that the effect of dynorphin A was prevented by aminopeptidases and neutral endopeptidase. Veratridine (30 µM) or 50 mM KCl produced MOR-1 internalization in the presence of peptidase inhibitors, but little or no internalization in their absence. These effects were attributed to opioid release, because they were abolished by the selective MOR antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH₂) and were Ca²⁺ dependent. The effect of veratridine was protected by phosphoramidon plus amastatin or captopril, but not by amastatin plus captopril or by phosphoramidon alone, indicating that released opioids are primarily cleaved by neutral endopeptidase, with a lesser involvement of aminopeptidases and dipeptidyl carboxypeptidase. Therefore, because the potencies of endomorphin-1 and endomorphin-2 to elicit internalization were unaffected by peptidase inhibitors, the opioids released by veratridine were not endomorphins. Confocal microscopy revealed that MOR-1-expressing neurons were in close proximity to terminals containing opioids with enkephalin-like sequences. These findings indicate that peptidases prevent the activation of extrasynaptic MOR-1 in dorsal horn neurons.

Key words: amastatin; aminopeptidase; captopril; dipeptidyl carboxypeptidase; dynorphin; endocytosis; endomorphin; endorphin; enkephalin; internalization; µ-opioid receptor; neutral endopeptidase; opioid; peptidase; phosphoramidon; rat; release; spinal cord

---

Copyright © 2003 Society for Neuroscience  0270-6474/03/2351847-12$05.00/0

This article has been cited by other articles:

				S. Hua, S. Hermanussen, L. Tang, G. R. Monteith, and P. J. Cabot The Neural Cell Adhesion Molecule Antibody Blocks Cold Water Swim Stress-Induced Analgesia and Cell Adhesion Between Lymphocytes and Cultured Dorsal Root Ganglion Neurons Anesth. Analg., December 1, 2006; 103(6): 1558 - 1564. [Abstract] [Full Text] [PDF]

				B. Song and J. C. G. Marvizon Dorsal Horn Neurons Firing at High Frequency, But Not Primary Afferents, Release Opioid Peptides that Produce {micro}-Opioid Receptor Internalization in the Rat Spinal Cord J. Neurosci., October 8, 2003; 23(27): 9171 - 9184. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help