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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 338, Issue 5, pp 553–559 | Cite as

Morphine tolerance and nonspecific subsensitivity of the longitudinal muscle myenteric plexus preparation of the guinea-pig to inhibitory agonists

  • David A. Taylor
  • Judith A. Leedham
  • Nancy Doak
  • William W. Fleming
Article

Summary

  1. 1.

    The sensitivity of the longitudinal smooth muscle/myenteric plexus (LM/MP) to agonists which reduce the amplitude of neurogenic contractions was studied in preparations obtained from animals implanted with either placebo or morphine (75 mg/pellet) pellets 7 days prior.

     
  2. 2.

    Tolerance or subsensitivity to morphine was observed following chronic treatment with morphine and was revealed as a rightward shift of the concentration-response curve to morphine. The degree of tolerance decayed modestly with time after removal from a morphine containing environment suggesting a time dependence for the loss of subsensitivity to morphine.

     
  3. 3.

    LM/MP preparations from animals pretreated with morphine also developed subsensitivity to the inhibitory effects of the purine analogue, 2-chloroadenosine. Subsensitivity to 2-chloroadenosine was seen as a parallel rightward shift of the concentration-response curve in morphine-tolerant preparations. The magnitude of the loss in sensitivity was comparable to that observed to morphine.

     
  4. 4.

    A reduction in sensitivity of the LM/MP following chronic treatment with morphine was also observed to the inhibitory effects of the alpha2 adrenoceptor agonists, clonidine and xylazine. In contrast to the results obtained with morphine and 2-chloroadenosine, the development of subsensitivity to alpha2 adrenoceptor agonists was characterized by a marked reduction in slope and a depression of the maximum response.

     
  5. 5.

    These data suggest that myenteric neurons possess spare receptors for morphine and 2-chloroadenosine but not for clonidine and xylazine. Furthermore, the studies support the idea that tolerance is associated with a general cellular change or adaptation which impacts on all of these inhibitory substances in such a way as to reduce their efficacy.

     

Key words

Opioid tolerance Subsensitivity Myenteric plexus Guinea-pig ileum Spare receptors 

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Copyright information

© Springer-Verlag 1988

Authors and Affiliations

  • David A. Taylor
    • 1
  • Judith A. Leedham
    • 1
  • Nancy Doak
    • 1
  • William W. Fleming
    • 1
  1. 1.Department of Pharmacology and ToxicologyWest Virginia University Health Sciences CenterMorgantownUSA

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