ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2003
Peptidases prevent mu-opioid receptor internalization in dorsal horn neurons by endogenously released opioids.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 51 citations in OpenAlex.
- Opiorphin: an endogenous human peptide with intriguing application in diverse range of pathologies.Inflammopharmacology · 2024Review
- Neuropeptide Y release in the rat spinal cord measured with Y1 receptor internalization is increased after nerve injury.Neuropharmacology · 2019Article
- Inflammation-associated changes in DOR expression and function in the mouse colon.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Sustained Suppression of Hyperalgesia during Latent Sensitization by μ-, δ-, and κ-opioid receptors and α2A Adrenergic Receptors: Role of Constitutive Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- The Emerging Role of Spinal Dynorphin in Chronic Pain: A Therapeutic Perspective.Annual review of pharmacology and toxicology · 2016Review
- Endothelin-converting enzyme 2 differentially regulates opioid receptor activity.British journal of pharmacology · 2015Article
- μ-Opioid receptor inhibition of substance P release from primary afferents disappears in neuropathic pain but not inflammatory pain.Neuroscience · 2014Article
- TGF-β and opioid receptor signaling crosstalk results in improvement of endogenous and exogenous opioid analgesia under pathological pain conditions.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Inhibiting the breakdown of endogenous opioids and cannabinoids to alleviate pain.Nature reviews. Drug discovery · 2012Review
- The Alzheimer's amyloid-degrading peptidase, neprilysin: can we control it?International journal of Alzheimer's disease · 2012Article
- Immunohistochemical localization of mu opioid receptor in the marginal division with comparison to patches in the neostriatum of the rat brain.Journal of biomedical science · 2011Article
- Cannabinoid CB1 receptor facilitation of substance P release in the rat spinal cord, measured as neurokinin 1 receptor internalization.The European journal of neuroscience · 2010Article
- Enkephalins, dynorphins, and beta-endorphin in the rat dorsal horn: an immunofluorescence colocalization study.The Journal of comparative neurology · 2009Article
- Acute inflammation induces segmental, bilateral, supraspinally mediated opioid release in the rat spinal cord, as measured by mu-opioid receptor internalization.Neuroscience · 2009Article
- Effects of veratridine and high potassium on micro-opioid receptor internalization in the rat spinal cord: stimulation of opioid release versus inhibition of internalization.Journal of neuroscience methods · 2008Article
- Inhibition of opioid release in the rat spinal cord by alpha2C adrenergic receptors.Neuropharmacology · 2008Article
- Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce mu-opioid receptor internalization in the presence of peptidase inhibitors.Brain research · 2008Article
- Chronic morphine use does not induce peripheral tolerance in a rat model of inflammatory pain.The Journal of clinical investigation · 2008Article
- Comparing analgesia and mu-opioid receptor internalization produced by intrathecal enkephalin: requirement for peptidase inhibition.Neuropharmacology · 2007Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
To evaluate the effect of peptidases on mu-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 alpha-neoendorphin, but not endomorphins or beta-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 microm) 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-NH(2)) and were Ca(2+) 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.
Indexed as
Identifiers
12629189PMC2464295W2123576957What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.