![[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}
|
|
|
|
|
||
C Kennedy and G Henderson
Department of Pharmacology, University of Cambridge, Great Britain.
The human SH-SY5Y neuroblastoma cell line displays morphological, neurochemical, and electrophysiological characteristics of sympathetic neurons. mu-Opioid receptors mediate inhibition of the N-type calcium current present in these cells. Here we have studied the effects of chronic incubation with morphine (1 microM for 3-7 days) in vitro on the inhibition of this current induced by mu-opioid agonists and noradrenaline. In untreated control cells the mu-opioid agonists and noradrenaline. In untreated control cells the mu-opioid agonists morphine (1 microM) and [D-Ala2,N-MePhe4,Gly-ol] enkephalin (DAMGO) (10 nM to 1 microM), and noradrenaline (10 nM to 10 microM) inhibited the calcium current to a similar extent. The maximal effects of DAMGO and noradrenaline were not additive. Chronic exposure to morphine had no effect on the maximum amplitude of the calcium current evoked or on its voltage sensitivity. However, the concentration-response curve to DAMGO was shifted to the right in a parallel manner, with a 7-fold increase in the IC50 value but no change in the maximum inhibition produced. In contrast, the maximum inhibition in response to morphine appeared to be substantially reduced. Noradrenaline inhibited the calcium current equally in untreated and morphine-tolerant cells. Thus, it is concluded that morphine-induced tolerance to inhibition of the N-type calcium current occurs at the single-cell level and is homologous to the mu- opioid receptor. Also, morphine appears to be an agonist of lower efficacy than DAMGO. The results are consistent with tolerance being due to a functional reduction in the mu-opioid receptor reserve, probably by disruption of the receptor/GTP-binding protein interaction.
This article has been cited by other articles:
|
|
 |
|
  J. T. Williams, M. J. Christie, and O. Manzoni Cellular and Synaptic Adaptations Mediating Opioid Dependence Physiol Rev, January 1, 2001; 81(1): 299 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shoji, J. Delfs, and J. T. Williams Presynaptic Inhibition of GABAB-Mediated Synaptic Potentials in the Ventral Tegmental Area during Morphine Withdrawal J. Neurosci., March 15, 1999; 19(6): 2347 - 2355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Jin, G. W. Terman, and C. Chavkin Kappa Opioid Receptor Tolerance in the Guinea Pig Hippocampus J. Pharmacol. Exp. Ther., April 1, 1997; 281(1): 123 - 128. [Abstract] [Full Text]
|
|
|
|
|
|
E. J. Wagner, G. Zhang, A. H. Lagrange, O. K. Rønnekleiv, and M. J. Kelly Tolerance to µ-Opioid Receptor Agonists but not Cross-tolerance to gamma -Aminobutyric AcidB Receptor Agonists in Arcuate A12 Dopamine Neurons with Chronic Morphine Treatment J. Pharmacol. Exp. Ther., February 1, 1997; 280(2): 1057 - 1064. [Abstract] [Full Text]
|
|
|
|
|
|
A. Bonci and J. T. Williams Increased Probability of GABA Release during Withdrawal from Morphine J. Neurosci., January 15, 1997; 17(2): 796 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Chieng and M. J. Christie Local Opioid Withdrawal in Rat Single Periaqueductal Gray Neurons In Vitro J. Neurosci., November 15, 1996; 16(22): 7128 - 7136. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
