![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 302, Issue 2, 568-576, August 2002
-D-glucuronide Suppresses Inhibitory
Synaptic Transmission in Rat Substantia Gelatinosa
University Centre for Neuroscience and Department of Pharmacology,
University of Alberta, Edmonton, Alberta, Canada
High doses of intrathecally applied morphine or
morphine-3
-D-glucuronide (M3G) produce allodynia and
hyperalgesia. Whole-cell patch-clamp recordings were made from
substantia gelatinosa neurons in transverse slices of adult rat lumbar
spinal cord to compare the actions of M3G with those of the µ-opioid
agonist, DAMGO
([D-Ala2,N-Met-Phe4,Gly-ol5]-enkephalin),
and the ORL1 agonist, nociceptin/orphanin FQ (N/OFQ). M3G
(1-100 µM) had little or no effect on evoked excitatory postsynaptic currents (EPSC) and no effect on postsynaptic membrane conductance. In
contrast, 1 µM DAMGO and 1 µM N/OFQ reduced the amplitude of evoked
EPSCs and activated an inwardly rectifying K+ conductance.
M3G did not attenuate the effect of DAMGO or N/OFQ on evoked EPSC
amplitude. However, 1 to 100 µM M3G reduced the amplitude of evoked
GABAergic and glycinergic inhibitory postsynaptic current (IPSC) by up
to 48%. This effect was naloxone-insensitive. The evoked IPSC was also
attenuated by DAMGO, but not by N/OFQ. Because M3G reduced the
frequency of tetrodotoxin-insensitive miniature IPSCs and
increased paired-pulse facilitation, it appeared to act presynaptically
to disinhibit substantia gelatinosa neurons. This effect, which does
not appear to involve µ-opioid or ORL1 receptors, may
contribute to the allodynia and hyperalgesia observed after intrathecal
application of high doses of morphine.
This article has been cited by other articles:
|
|
 |
|
  J. Sandkuhler Models and Mechanisms of Hyperalgesia and Allodynia Physiol Rev, April 1, 2009; 89(2): 707 - 758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. van de Wetering, N. Zelcer, A. Kuil, W. Feddema, M. Hillebrand, M. L. H. Vlaming, A. H. Schinkel, J. H. Beijnen, and P. Borst Multidrug Resistance Proteins 2 and 3 Provide Alternative Routes for Hepatic Excretion of Morphine-Glucuronides Mol. Pharmacol., August 1, 2007; 72(2): 387 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Balasubramanyan, P. L. Stemkowski, M. J. Stebbing, and P. A. Smith Sciatic Chronic Constriction Injury Produces Cell-Type-Specific Changes in the Electrophysiological Properties of Rat Substantia Gelatinosa Neurons J Neurophysiol, August 1, 2006; 96(2): 579 - 590. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Zelcer, K. van de Wetering, M. Hillebrand, E. Sarton, A. Kuil, P. R. Wielinga, T. Tephly, A. Dahan, J. H. Beijnen, and P. Borst Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception PNAS, May 17, 2005; 102(20): 7274 - 7279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Moran, W. F. Colmers, and P. A. Smith Opioid-Like Actions of Neuropeptide Y in Rat Substantia Gelatinosa: Y1 Suppression of Inhibition and Y2 Suppression of Excitation J Neurophysiol, December 1, 2004; 92(6): 3266 - 3275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Vaughan and M. Connor In Search of a Role for the Morphine Metabolite Morphine-3-Glucuronide Anesth. Analg., August 1, 2003; 97(2): 311 - 312. [Full Text] [PDF]
|
|
|
|
|
|
K. Hemstapat, G. R. Monteith, D. Smith, and M. T. Smith Morphine-3-Glucuronide's Neuro-Excitatory Effects Are Mediated via Indirect Activation of N-Methyl-D-Aspartic Acid Receptors: Mechanistic Studies in Embryonic Cultured Hippocampal Neurones Anesth. Analg., August 1, 2003; 97(2): 494 - 505. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
