Neurochemical Research

, Volume 2, Issue 5, pp 581–593 | Cite as

Calcium content and binding in synaptosomal subfractions during chronic morphine treatment

  • David H. Ross


Chronic exposure to morphine in mice produced an increase in Ca2+ content of synaptosomes, synaptic plasma membranes (SPM), and synaptic vesicles. Ca2+ binding capacity was significantly reduced in tolerant SPM fractions. Naloxone significantly reversed the increased calcium content and reduced binding capacity of SPM when administered to 72-h-treated mice. Scatchard analysis of binding curves reveals three distinct classes of Ca2+ binding sites. During tolerance, the high- and low-affinity sites exhibit a reduced capacity to bind calcium, which may be reversed by in vivo and in vitro administration of naloxone. The increase in SPM and synaptic vesicle calcium content may reflect adaptive changes in the cell membrane during tolerance development, which may contribute to changes in neurotransmitter and second messenger function.


Calcium Morphine Naloxone Binding Capacity Chronic Exposure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Berl, S., Puszkin, S., andNicklos, W. J. 1973. Actomyosin-like protein in brain. Science 179:441–446.Google Scholar
  2. 2.
    Blaustein, M. P. 1975. Effects of potassium veratridine and scorpion neuron on calcium accumulation and transmitter release by nerve terminalsin vitro. J. Physiol. 247:627–655.Google Scholar
  3. 3.
    Cardenas, H. L., andRoss, D. H. 1975. Morphine induced calcium depletion in discrete regions of rat brain. J. Neurochem. 24:487–493.Google Scholar
  4. 4.
    Cardenas, H. L., andRoss, D. H. 1976. Calcium depletion of synaptosomes after morphine treatment. Br. J. Pharmacol. 57:521–526.Google Scholar
  5. 5.
    Collier, H. O. J. 1966. Tolerance, physical dependence and receptors: A theory of the genesis of tolerance and physical dependence through drug induced changes in the number of receptors. Adv. Drug Res. 3:171–188.Google Scholar
  6. 6.
    Clouet, D. H., andIwatsubo, E. 1975. Mechanism of tolerance to and dependence on narcotic analgesic drugs. Ann. Rev. Pharmacol. 15:49–71.Google Scholar
  7. 7.
    Cotman, C. W., andMatthews, D. A. 1971. Synaptic plasma membranes from rat brain: Isolation and characterization. Biochim. Biophys. Acta 249:380–394.Google Scholar
  8. 8.
    Harris, R. A., Loh, H. H., andWay, E. L. 1975. Effects of divalent cations, cation chelators and an ionophore on morphine analgesia and tolerance. J. Pharmacol. Exp. Ther. 195:488–498.Google Scholar
  9. 9.
    Harris, R. A., Iwamoto, E. T., Loh, H. H., andWay, E. L., 1975. Analgesic Effects of lanthanum: Cross tolerance with morphine. Brain Res. 100:221–225.Google Scholar
  10. 10.
    Harris, R. A., Loh, H. H., andWay, E. L., 1976. Antinociceptive effects of lanthanum and cerium in nontolerant and morphine tolerant-dependent animals. J. Pharmacol. Exp. Ther. 196:288–296.Google Scholar
  11. 11.
    Hemminki, K. 1974. Ca++ binding to brain plasma membranes. Biochim. Biophys. Acta 363:202–210.Google Scholar
  12. 12.
    Kakunaga, T., Kaneto, H., andHano, K. 1966. Pharmacologic studies on analgesics. VII. Significance of the calcium ion in morphine analgesia. J. Pharmacol. Exp. Ther. 153:134–141.Google Scholar
  13. 13.
    Klee, W. A., Sharma, S. K., andNirenberg, M. 1975. Opiate receptors as regulators of adenylate cyclase. Life Sci. 16:1869–1974.Google Scholar
  14. 14.
    Lowry, O. H., Rosebrough, N. L., Farr, A. J., andRandall, R. J. 1951. Protein measurement with the Folin-Phenol reagent. J. Biol. Chem. 193:265.Google Scholar
  15. 15.
    Minneman, K. P., andIverson, L. L. 1976. Enkaphalin and opiate narcotics increase cyclic GMP accumulation in slices of rat neostriatum. Nature 262:313–314.Google Scholar
  16. 16.
    Morgenroth, V. H., Boadle-Biber, M. C., andRoth, R. H. 1975. Activation of tyrosine hydroxylase from central noradrenergic neurons by calcium. Mol. Pharmacol. 11:427–435.Google Scholar
  17. 17.
    Olson, D. R., Kon, C., andBreckenridge, B. McL. 1976. Calcium ion effects on guanylate cyclase of brain. Life Sci. 18:935–940.Google Scholar
  18. 18.
    Racogni, G., Zsilla, G., Guidotti, A., andCosta, E. 1976. J. Pharm. Pharmacol. 28:258–260.Google Scholar
  19. 19.
    Ross, D. H. 1975. Tolerance to morphine-induced calcium depletion in regional brain areas: Characterization with reserpine and protein synthesis inhibitors. Br. J. Pharmacol. 55:431–437.Google Scholar
  20. 20.
    Ross, D. H. 1976. Calcium metabolism after acute and chronic ethanol administration. Ann. NY Acad. Sci. (in press, 1976).Google Scholar
  21. 21.
    Ross, D. H., andCardenas, H. L. 1977. Effects of levorphanol on Ca++ binding to synaptic membranesin vitro. Life Sci. 20:1455–1462.Google Scholar
  22. 22.
    Reis, D. J., Hess, P., andAzmitia, E. C. 1970. Changes in enzymes subserving catecholomine metabolism in morphine tolerance and withdrawal in rats. Brain Res. 20:309–318.Google Scholar
  23. 23.
    Scatchard, G. 1949. The attraction of protein for small molecules and ions. Ann. NY Acad. Sci. 51:660–672.Google Scholar
  24. 24.
    Sharma, S. K., Nirenberg, M., andKlee, W. A. 1975. Morphine receptors as regulators of adenylate cyclase activity. Proc. Natl. Acad. Sci. 72:590–594.Google Scholar
  25. 25.
    Shlatz, L., andMarinetti, G. V. 1972. Calcium binding to the rat brain plasma membrane. Biochim. Biophys. Acta 290:70–83.Google Scholar
  26. 26.
    Snedecor, G. W., andCochran, W. G. 1969. Statistical Methods, 6th Ed., Iowa State University Press, Ames, Iowa.Google Scholar
  27. 27.
    Way, E. L., Loh, H. H., andShen, F. 1969. Simultaneous quantitative assessment of morphine tolerance and physical dependence. J. Pharmacol. Exp. Ther. 167:1–8.Google Scholar
  28. 28.
    Weiss, G. B. 1974. Cellular pharmacology of lanthanum. Ann. Rev. Pharm. 14:343–354.Google Scholar
  29. 29.
    Whittaker, V. P., Michaelson, I. A., andKirkland, R. J. 1964. The separation of synaptic vesicles from nerve ending particles (synaptosomes). Biochem. J. 90:293–303.Google Scholar
  30. 30.
    Ross, D. H., Lynn, S. C. Jr., andCardenas, H. L. 1976. Selective control of calcium levels by naloxone. Life Sci. 18:789–796.Google Scholar

Copyright information

© Plenum Publishing Corporation 1977

Authors and Affiliations

  • David H. Ross
    • 1
  1. 1.Departments of Pharmacology and PsychiatryThe University of Texas Health Science CenterSan Antonio

Personalised recommendations