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The effect of ethanol on the biosynthesis and regulation of opioid peptides

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Summary

Alcoholism and alcohol abuse are serious health problems. Alcohol is known to influence the activity of a number of biological systems, for example the hormonal and neuronal systems. One of the biological systems whose activity is greatly influenced by alcohol is the endogenous opiate system. Alcohol modifies the function of both opiate receptors and opioid peptides. In fact it has been proposed that many of the effects of ethanol are mediated by its effects on the endogenous opiate system. This review will present results from various laboratories on the effects of acute and chronic ethanol treatments on various species, and on the release, biosynthesis and post-translational processing of the endorphins, enkephalins and dynorphins, the three known families of endogenous opioid peptides. Furthermore, the effect of acute and chronic ethanol consumption on the β-endorphin system in man, and the possible implications of the functional activity of the endogenous opiate system for the genetic predisposition to alcoholism will be discussed.

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Abbreviations

POMC:

pro-opiomelanocortin

β-EP:

β-endorphin

β-EPLPS:

β-endorphin like peptides

β-LPH:

β-lipotropin

NIL:

neurointermediate lobe of the pituitary gland

AL:

anterior lobe of the pituitary gland

irβ-EP:

immunoreactive β-endorphin

ACTH:

adrenal corticotropin

CRF:

corticotropin releasing factor

References

  1. Akil, H., Shiomi, H., and Matthews, J., Induction of intermediate pituitary by stress: synthesis and release of a nonopioid form of β-endorphin. Science227 (1985) 424–426.

    Article  CAS  PubMed  Google Scholar 

  2. Akil, H., Watson, S. J., Young, E., Lewis, M. E., Khachaturian, H., and Walker, J. M., Endogenous opioids: Biology and function. A. Rev. Neurosci.7 (1984) 223–255.

    Article  CAS  Google Scholar 

  3. Akil, H., and Watson, S. J., Immunocytochemical localization of proopiomelanocortin derived peptides in the adult spinal cord. Brain Res.378 (1986) 28–35.

    Article  PubMed  Google Scholar 

  4. Akil, H., Young, E., and Watson, S. J., Opiate binding properties of naturally occurring N and C-terminus modified β-endorphin. Peptides2 (1981) 289–292.

    Article  CAS  PubMed  Google Scholar 

  5. Altshuler, H. L., Philips, P. E., and Feinhandler, D. E., Alteration of ethanol self-administration by naltrexone. Life Sci.26 (1980) 679–688.

    Article  CAS  PubMed  Google Scholar 

  6. Badawy, A. A. B., Williams, D. L., and Evans, M., Role of tyrosine in the acute effects of ethanol on rat brain catecholamine synthesis. Pharmac. Biochem. Behav.18, Suppl. 1 (1983) 389–396.

    Article  CAS  Google Scholar 

  7. Berkenbosch, F., Tilders, F. J. H., and Vermes, I., β-Adrenoceptor activation mediates stress-induced secretion of β-endorphin-related peptides from intermediate but not anterior pituitary. Nature305 (1983) 237–239.

    Article  CAS  PubMed  Google Scholar 

  8. Blum, K., Briggs, A. H., Elston, S. F. A., DeLallo, L., and Sheridon, P. J., Reduced leucine-enkephalin-like immunoreactive substance in hamster basal ganglia after long-term ethanol exposure. Science216 (1982) 1424–1427.

    Article  Google Scholar 

  9. Blum, K., and Topel, H., Opioid peptides and alcoholism: Genetic deficiency and chemical management. Funct. Neurol.1 (1986) 71–83.

    CAS  PubMed  Google Scholar 

  10. Branchey, M., Rauscher, G., and Kissin, B., Modification in the response to alcohol following the establishment of physical dependence. Psychopharmacologia22 (1971) 314–322.

    Article  CAS  PubMed  Google Scholar 

  11. Charness, M. E., Gordon, A. S., and Diamond, I., Ethanol modulation of opiate receptors in cultured neural cells. Science222 (1983) 1246–1248.

    Article  CAS  PubMed  Google Scholar 

  12. Chavkin, C., James, I. F., and Goldstein, A., Dynorphin is a specific endogenous ligand of theK opioid receptor. Science215 (1982) 413–415.

    Article  CAS  PubMed  Google Scholar 

  13. Cheng, S. S., and Tseng, L. F., Chronic administration of ethanol on pituitary and hypothalamic β-endorphin in rats and golden hamsters. Pharmac. Res. Commun.14 (1982) 1001–1008.

    Article  CAS  Google Scholar 

  14. Corbett, A. D., Patterson, S. J., McKight, A. I., Magnan, J., and Kosterlitz, H. W., Dynorphin 1–8 and Dynorphin 1–9 are ligands for theK-subtype of opiate receptors. Nature299 (1982) 79–81.

    Article  CAS  PubMed  Google Scholar 

  15. Crine, P., Gianoulakis, C., Seidah, N. G., Gossard, F., Pezalla, P. D., Lis, M., and Chrétien, M., Biosynthesis of β-endorphin from β-lipotropin and a larger molecular weight precursor in rat pars intermedia. Proc. natl Acad. Sci. USA75 (1978) 4719–4723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Dave, J. R., Giden, L. G., Karanian, J. W., and Eskay, R. L., Ethanol exposure decreases pituitary corticotropin-releasing factor binding, adenylate cyclase, pro-opiomelanocortin biosynthesis and plasma β-endorphin levels in the rat. Endocrinology118 (1986) 280–286.

    Article  CAS  PubMed  Google Scholar 

  17. Davies, V. G., and Walsh, M. J., Alcohol, amines and alkaloids: a possible basis for alcohol addiction. Science167 (1970) 1005–1007.

    Article  Google Scholar 

  18. Delbende, C., Jegou, S., Tranchand-Bunel, D., Pelletier, G., and Vaudry, H., Hypothalamic α-melanocyte-stimulating hormone (α-MSH) is not under dopaminergic control. Brain Res.423 (1987) 203–212.

    Article  CAS  PubMed  Google Scholar 

  19. Dores, R. M., Jain, M., and Akil, H., Characterization of the forms of β-endorphin and α-MSH in the caudal medulla of the rat and guinea pig. Brain Res.377 (1986) 251–260.

    Article  CAS  PubMed  Google Scholar 

  20. Eipper, B. A., and Mains, R. E., Existence of a common precursor to ACTH and endorphin in the anterior and intermediate lobes of the rat pituitary. J. supramolec. Struct.8 (1978) 247–262.

    Article  CAS  Google Scholar 

  21. Gianoulakis, C., Long-term ethanol alters the binding of3H-opiates to brain membranes. Life Sci.33 (1983) 725–733.

    Article  CAS  PubMed  Google Scholar 

  22. Gianoulakis, C., and Barcomb, A., Effect of acute ethanol in vivo and in vitro on the β-endorphin system in the rat. Life Sci.40 (1987) 19–28.

    Article  CAS  PubMed  Google Scholar 

  23. Gianoulakis, C., Chan, J. S. D., Kalant, H., and Chrétien, M., Chronic ethanol treatment alters the biosynthesis of β-endorphin by the rat neurointermediate lobe. Can. J. Physiol. Pharmac.61 (1983) 967–976.

    Article  CAS  Google Scholar 

  24. Gianoulakis, C., and Chrétien, M., Endorphins in fetomaternal physiology, in: Principles of Medical Therapy, pp. 162–172. Ed. N. Gleicher. Plenum, New York 1985.

    Chapter  Google Scholar 

  25. Gianoulakis, C., and Gupta, A., Inbred strains of mice with variable sensitivity to ethanol exhibit differences in the content and processing of β-endorphin. Life Sci.39 (1986) 2315–2325.

    Article  CAS  PubMed  Google Scholar 

  26. Gianoulakis, C., Hutchison, W. D., and Kalant, H., Effects of ethanol treatment and withdrawal on biosynthesis and processing of proopiomelanocortin by the rat neurointermediate lobe. Endocrinology122 (1988) 817–825.

    Article  CAS  PubMed  Google Scholar 

  27. Gianoulakis, C., Woo, N., Drouin, J. N., Seidah, N. G., Kalant, H., and Chrétien, M., Biosynthesis of β-endorphin by the neurointermediate lobes from rats treated with morphine or alcohol. Life Sci.29 (1981) 1973–1982.

    Article  CAS  PubMed  Google Scholar 

  28. Gambert, S. R., Pontjer, C. H., and Barboriak, J. J., Effect of ethanol consumption on central nervous system (CNS) beta-endorphin and ACTH. Horm. Metab. Res.13 (1981) 242–243.

    Article  CAS  PubMed  Google Scholar 

  29. Ganazzani, A., Nappi, G., Facchinetti, F., Sinforiani, E., Petraglia, F., and Savoldi, F., Central deficiency of β-endorphin in alchol addicts. Clin. Endocr. Metab.55 (1982) 583–586.

    Article  Google Scholar 

  30. Gibbs, D. M., Stewart, R. D., Vale, W., Rivier, J., and Yen, S. S. C., Synthetic corticotropin-releasing factor stimulates secretion of immunoreactive beta-endorphin/beta-lipotropin and ACTH by human fetal pituitaries in vitro. Life Sci.32 (1982) 547–550.

    Article  Google Scholar 

  31. Goldstein, D. B., Chin, J. H., and Lyon, R. C., Disordering of spinlabeled mouse brain membranes. Correlation with genetically determined ethanol sensitivity of mice. Proc. natl Acad. Sci. USA79 (1982) 4231–4233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Guillemin, R., Vargo, T., Rossier, J., Minick, S., Ling, N., Rivier, C., Vale, W., and Bloom, F., β-Endorphin and adrenocorticotropin are secreted concomitantly by the pituitary gland. Science196 (1977) 1367–1369.

    Article  Google Scholar 

  33. Ham, J., and Smyth, D. G., β-Endorphin processing in pituitary and brain is sensitive to haloperiodol stimulation. Neuropeptides5 (1985) 497–500.

    Article  CAS  PubMed  Google Scholar 

  34. Harris, R. A., and Schrogder, F., Ethanol and the physical properties of brain membranes. Fluorescence studies. Molec. Pharmac.20 (1981) 128–137.

    CAS  Google Scholar 

  35. Hughes, J., Smith, T., Kosterlitz, H. W., Fothergill, L. A., Morgan, B. A., and Morris, H. R., Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature258 (1975) 577–579.

    Article  CAS  PubMed  Google Scholar 

  36. Hutchison, W. D., Gianoulakis, C., and Kalant, H., Effects of ethanol withdrawal on β-endorphin levels in rat brain and pituitary. Pharmac. Biochem. Behav.30 (1988) 933–939.

    Article  CAS  Google Scholar 

  37. Jenkins, J. S., and Conolly, J., Adrenocortical response to ethanol in man. Br. med. J.2 (1968) 804–805.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kakidani, H., Furutami, Y., Takahashi, H., Noda, M., Mozimoto, Y., Hirose, T., Asai, M., Inayama, S., Nakanishi, S., and Numa, S., Cloning and sequence analysis of CDNA for porcine β-neoendorphin/dynorphin precursor. Nature298 (1982) 245–249.

    Article  CAS  PubMed  Google Scholar 

  39. Kalant, H., Alcohol withdrawal syndrome in the human: Comparison with animal models, in: Alcohol Intoxication and Withdrawal. Vol. 111 B, pp. 57–63. Ed. M. M. Gross. Plenum Press, New York 1977.

    Chapter  Google Scholar 

  40. Khachaturian, H., Watson, S. J., Lewis, M. E., Coy, D., Goldstein, A., and Akil, H., Dynorphin immunocytochemistry in the rat central nervous system. Peptides3 (1982) 941–954.

    Article  CAS  PubMed  Google Scholar 

  41. Khanna, J. M., Kalant, H., and Bustos, G., Effects of chronic intake of ethanol on the rate of ethanol metabolism. II. Influence of sex and of schedule of ethanol administration. Can. J. Physiol. Pharmac.45 (1967) 777–785.

    Article  CAS  Google Scholar 

  42. Khanna, J. M., Le, A. D., Kalant, H., and Leblanc, A. E., Cross-tolerance between ethanol and morphine with respect to their hypothermic effects. Eur. J. Pharmac.59 (1979) 145–149.

    Article  CAS  Google Scholar 

  43. Keith, L. D., Crabbe, J., Robertson, L. M., and Kendall, J. W., Ethanol stimulated endorphin and corticotropin secretion in vitro. Brain Res.367 (1986) 222–229.

    Article  CAS  PubMed  Google Scholar 

  44. Kiianmaa, K., and Tabakoff, B., Neurochemical correlates of tolerance and strain differences in the neurochemical effects of ethanol. Pharmac. Biochem. Behav.18, Suppl. 1 (1983) 383–388.

    Article  CAS  Google Scholar 

  45. Kilpatrick, D. L., and Rosenthal, J. L., The pro-enkephalin gene is widely expressed within the male and female reproductive systems of the rat and hamster. Endocrinology119 (1986) 370–374.

    Article  CAS  PubMed  Google Scholar 

  46. Leppaluoto, J., Rapeli, M., Varis, R., and Ranta, T., Secretion of anterior pituitary hormones in man: Effects of ethyl alcohol. Acta physiol. scand.95 (1975) 400–406.

    Article  CAS  PubMed  Google Scholar 

  47. Lis, M., Larivière, N., Maurice, G., Julesz, J., Seidah, N., and Chrétien, M., Concomitant changes of ACTH, β-endorphin and N-terminal portion of pro-opiomelanocortin in rats. Life Sci.30 (1982) 1159–1164.

    Article  CAS  PubMed  Google Scholar 

  48. Liotta, A. S., Loudes, C., McKelvy, J. F., and Krieger, D. T., Biosynthesis of precursor corticotropin/endorphin-corticotropin-, α-melanotropin-, β-lipotropin-, and β-endorphin-like material by cultured neonatal rat hypothalamic neurons. Proc. natl Acad. Sci. USA77 (1980) 1880–1884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Locafelli, V., Petraglia, F., Panalva, A., and Panerai, A. E., Effect of dopaminergic drugs on hypothalamic and pituitary immunoreactive β-endorphin concentrations in the rat. Life Sci.33 (1983) 1711–1717.

    Article  Google Scholar 

  50. Lolait, S. J., Autelitano, D. J., Lim, A. T. W., Smith, A. I., Toh, B. H., and Funder, J. W., Ovarian immunoreactive β-endorphin and estrous cycle in the rat. Endocrinology117 (1985) 161–168.

    Article  CAS  PubMed  Google Scholar 

  51. Lord, J. A. H., Waterfield, A. A., Hughes, J., and Kosterlitz, H. W., Endogenous opioid peptides. Multiple agonists and receptors. Nature267 (1976) 495–499.

    Article  Google Scholar 

  52. Martin, W. R., Eades, C. G., Thompson, J. A., Huppler, R. E., and Gilbert, P. E., The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. J. Pharmac. exp. Ther.197 (1976) 517–532.

    CAS  Google Scholar 

  53. Merry, J., and Marks, V., Plasma hydrocortisone response to ethanol in chronic alcoholics. Lancet1 (1969) 921.

    Article  CAS  PubMed  Google Scholar 

  54. Naber, D., Soble, M. G., and Pickar, D., Ethanol increases opioid activity in plasma of normal volunteers. Pharmacopsychiatry14 (1981) 160–161.

    Article  CAS  Google Scholar 

  55. Nakanishi, S., Inoue, A., Kita, T., Nakamura, M., Chang, A. C. T., Cohen, N. S., and Numa, S., Nucleotide sequence of cloned cDNA for bovine corticotropin-β-lipotropin precursor. Nature278 (1979) 423–427.

    Article  CAS  PubMed  Google Scholar 

  56. Noda, M., Teranishi, Y., Takahashi, H., Toyosato, M., Notake, M., Shigetada, N., and Numa, S., Isolation and structural organization of the human pre-proenkephalin gene. Nature297 (1982) 431–434.

    Article  CAS  PubMed  Google Scholar 

  57. Nussbaum, S. R., Carr, D. B., Bergland, R. M., Kliman, B., Fisher, J., Reiner, B., Kleshinski, S., and Rosenblatt, M., Dynamics of cortisol and endorphin responses to graded doses of synthetic ovine CRF in sheep. Endocrinology112 (1983) 877–879.

    Article  Google Scholar 

  58. Przewlocki, R., Höllt, V., Voight, K. H., and Herz, A., Modulation of in vitro release of β-endorphin from the separate lobes of the rat pituitary. Life Sci.24 (1979) 1601–1608.

    Article  CAS  PubMed  Google Scholar 

  59. Redei, E., Branch, J. B., and Taylor, A. N., Direct effect of ethanol on adrenocorticotropin (ACTH) release in vitro. J. Pharmac. exp. Ther.237 (1986) 59–64.

    CAS  Google Scholar 

  60. Rivier, C., Bruhn, T., and Vale, W., Effect of ethanol on the hypothalamic-pituitary-adrenal axis in the rat: role of corticotropin-releasing factor (CRF). J. Pharmac. exp. Ther.229 (1984) 127–131.

    CAS  Google Scholar 

  61. Ross, D. H., Selective action of alcohols on cerebral calcium levels. Ann. N.Y. Acad. Sci.273 (1976) 280–294.

    Article  CAS  PubMed  Google Scholar 

  62. Savoldi, F., Opioid peptides in alcoholics, in: Central and Peripheral Endorphins, pp. 333–338. Eds E. E. Müller and A. Genazzani. Raven Press, New York 1984.

    Google Scholar 

  63. Schultzberg, M., Hökfelt, T., Lundberg, J. M., Terenius, L., Elfvin, L. G., and Elde, R., Enkephalin-like immunoreactivity in nerve terminals in sympathetic ganglia and adrenal medulla and in adrenal medullary gland cells. Acta physiol. scand.103 (1978) 475–477.

    Article  CAS  PubMed  Google Scholar 

  64. Schulz, R., Wuster, M., Duka, T., and Herz, A., Acute and chronic ethanol treatment changes endorphin levels in brain and pituitary. Psychopharmacology68 (1980) 221–227.

    Article  CAS  PubMed  Google Scholar 

  65. Seizinger, B. R., Bovermann, K., Maysinger, D., Höllt, V., and Herz, A., Differential effects of acute and chronic ethanol treatment on particular opioid peptide systems in discrete regions of rat brain and pituitary. Pharmac. Biochem. Behav.18 (1983) 361–369.

    Article  CAS  Google Scholar 

  66. Seizinger, B. R., Bovermann, K., Höllt, V., and Herz, A., Enhanced activity of the endorphinergic system in the anterior and neurointermediate lobe of the rat pituitary gland after chronic treatment with ethanol liquid diet. J. Pharmac. exp. Ther.230 (1984) 455–461.

    CAS  Google Scholar 

  67. Seizinger, B. R., Höllt, V., and Herz, A., Effects of chronic ethanol treatment on the in vitro biosynthesis of pro-opiomelanocortin and its post-translational processing to β-endorphin in the intermediate lobe of the rat pituitary. J. Neurochem.43 (1984) 607–613.

    Article  CAS  PubMed  Google Scholar 

  68. Shuckit, M. A., Differences in plasma cortisol after ingestion of ethanol in relatives of alcoholics and controls: Preliminary results. J. clin. Psychiat.45 (1984) 374–376.

    Google Scholar 

  69. Triana, E., Richard, J. F., and Strokes, P. E., The relationship between endorphins and alcohol induced sub-cortical activity. Am. J. Psychiat.127 (1980) 491–493.

    Google Scholar 

  70. Tabakoff, B., Jaffe, R. C., and Ritzmann, R. F., Corticosterone concentrations in mice during ethanol drinking and withdrawal. J. Pharm. Pharmac.30 (1978) 371–374.

    Article  CAS  Google Scholar 

  71. Vermes, I., Mulder, G. H., Smelik, P. G., and Tilders, F. J. H., Differential control of β-endorphin/β-lipotropin secretion from anterior and intermediate lobes of the rat pituitary gland in vitro. Life Sci.27 (1980) 1761–1768.

    Article  CAS  Google Scholar 

  72. Vermes, I., Tilders, F. J. H., and Stoof, J. C., Dopamine inhibits the release of immunoreactive β-endorphin from rat hypothalamus in vitro. Brain Res.326 (1985) 41–46.

    Article  CAS  PubMed  Google Scholar 

  73. Wolter, H. J., Ultrastructural evidence for β-endorphin-like immunoreactivity in the nervous system of the rat duodenum. Brain Res.334 (1985) 194–199.

    Article  CAS  PubMed  Google Scholar 

  74. Wüster, M., Schjulz, R., and Herz, A., The direction of opioid agonists towards μ−δ and ε receptors in the rat vas deferens of the mouse and the rat. Life Sci.27 (1980) 163–170.

    Article  PubMed  Google Scholar 

  75. Zakarian, S., and Smyth, D. G., Distribution of β-endorphin related peptides in rat pituitary and brain. Biochem. J.202 (1982) 561–571.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Gianoulakis, C. The effect of ethanol on the biosynthesis and regulation of opioid peptides. Experientia 45, 428–435 (1989). https://doi.org/10.1007/BF01952024

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