Skip to main content
SpringerLink
Log in

Effect of nicotine on mRNA levels encoding opioid peptides, vasopressin and α3 nicotinic receptor subunit in the rat

  • Original Article
  • Published:
The clinical investigator Aims and scope Submit manuscript

Summary

The effect of acute and chronic nicotine treatment of rats on the mRNA levels coding for the three opioid peptide precursors, for provasopressin and for the a3 subunit of nicotinic receptors in brain, pituitary and/or adrenal medulla of rats was investigated. Nicotine was found to increase the levels of proenkephalin mRNA in the adrenal medulla, but did not affect the levels of PENK mRNA in striatum, hypothalamus and hippocampus. The mRNA levels of prodynorphin were increased together with that of provasopressin in the hypothalamus after nicotine, whereas the prodynorphin mRNA levels in the hippocampus and the striatum remained unchanged. Nicotine treatment resulted in an increase in the pro-opiomelanocortin mRNA levels in the anterior pituitary and in a decrease in the intermediate pituitary, but did not change the levels of pro-opiomelanocortin mRNA in the hypothalamus. The levels of mRNA coding for the α3 subunit of nicotinic receptors in the hypothalamus and the adrenal medulla remained unchanged. The increase in the prodynorphin and provasopressin mRNA levels in the hypothalamus was most pronounced 1 day after s.c. application of two doses of 0.4 mg/kg nicotine (about 100% above control). A smaller increase in mRNA concentrations (about 30%) was found after tonic infusion of the drug for 4 days (4 mg/kg per day), whereas no change was observed after tonic infusion of nicotine for 7 and 14 days indicating the development of complete tolerance. The increase in proenkephalin mRNA levels in the adrenal medulla was highest after the short-term application of nicotine (about 150% above control). Less, but still significant increases in the mRNA levels (about 40%) were also seen after 7 and 14 days of tonic nicotine administration suggesting that no complete desensitization is developing to the effect of nicotine. This desensitization appeared to be less pronounced when the drug was applied in a pulsatile manner using minipumps, since a high increase in the PENK mRNA levels (100% above control levels) was observed after intermittent infusion of nicotine (six boli per day of 1 mg/kg for 7 days). These findings demonstrate that nicotine can alter gene expression of opioid peptides and vasopressin in certain rat tissues, and that the mode of drug administration plays an important role in this effect of nicotine. The possibility that the ‘pulsatile’ administration of nicotine by cigarette smokers may also result in an altered expression of opioid peptide genes in humans is discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

PENK:

proenkephalin

POMC:

pro-opiomelanocortin

MSH:

melanocyte stimulating hormone

PDYN:

prodynorphin

CRF:

corticotropin releasing factor

References

  1. Andersson K, Siegel R, Fuxe K, Eneroth P (1983) Intravenous injection of nicotine induce very rapid and diserete reductions of hypothalamic catecholamine levels associated with increases of ACTH, vasopressin and prolactin secretin. Acta Physiol Scan 118:35–40.

    Article  CAS  Google Scholar 

  2. Auffray C, Rougeon F (1980) Purification of mouse immunoglobulin heavy chain mRNAs from total myeloma tumor RNA. Eur J Biochem 107:303–312.

    Article  CAS  PubMed  Google Scholar 

  3. Calogero AE, Galucci WT, Bernardini R, Saoutis C, Gold PW, Chrousos GP (1988) Effect of cholinergic agonists and antagonists on rat hypothalmic corticotropin-releasing hormone secretion in vitro. Neuroendocrinology 47:303–308.

    Article  CAS  PubMed  Google Scholar 

  4. Cam AE, Basset Jr, Carirneross KD (1979) The action of nicotine on the pituitary-adrenal-cortical axis. Arch Int Pharmacodyn Ther 237:49–66.

    CAS  PubMed  Google Scholar 

  5. Castro de Souza B, Rocha E, Silva M (1977) The release of vasopressin by nicotine: further studies on its site of action. J Physiol 265:297–311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Conte-Devolx, Oliver B, Girand C, Gillioz P, Castanas E, Lissitzky JC, Boudouresque F, Millet Y (1981) Effect of nicotine on in vivo secretion of melanocorticotrophic hormones in the rat. Life Sci 28:1067–1073.

    Article  CAS  PubMed  Google Scholar 

  7. Damsma G, Westerink BHC, de Vries JB, Horn AS (1988) The effect of systemically applied cholinergic drugs on the striatal release of dopamine and its metabolites, as determined by automated brain dialysis in conscious rats. Neurosci Lett 89:349–354.

    Article  CAS  PubMed  Google Scholar 

  8. Deneris ES, Connoly J, Rogers SW, Duvoisin R (1991) Pharmacological and functional diversity of neuronal nicotinic acetylcholine receptors. Trends Pharmacol Sci 12:34–40.

    Article  CAS  PubMed  Google Scholar 

  9. Fehr S, Schmale H, Richter D (1989) Differential polyadenylation of the mutant vasopressin mRNA during development of Brattleboro rats. Biochem Biophys Res Commun 158:555–561.

    Article  CAS  PubMed  Google Scholar 

  10. Fuxe K, Andersson K, Härfstrand A, Eneroth P, Perez de la Mora P, Agnatio LF (1990) Effects of nicotine on synaptic transmission in the brain. In: Wonnacott S, Russel MAH, Stolerman IP, (eds) Nicotine psychopharmacology: molecular, cellular behavioural aspects. Oxford University Press, Oxford, pp 194–225.

    Google Scholar 

  11. Goldman D, Deneris E, Luyten W, Kochhar A, Patrick J, Heinemann S (1987) Members of a nicotinic acetylcholine receptor gene family are expressed in different regions of the mammalian central nervous system. Cell 48:965–973.

    Article  CAS  PubMed  Google Scholar 

  12. Höllt V, Horn G (1989) Nicotine and opioid peptides. In: Nordberg A, Fuxe K, Holmstedt B, Sundwall A (eds) Progress in brain research. (vol 79) Elsevier, Amsterdam, pp 187–193.

    Google Scholar 

  13. Höllt V, Horn G (1991) Nicotine induces opioid peptide gene expression in hypothalamus and adrenal medulla of rats. In: Adlkofer F, Thurau K (eds) Effects of nicotine on biological systems. Birkhäuser, Basel, pp 273–283.

    Chapter  Google Scholar 

  14. Höllt V, Haarmann I, Seizinger BR, Herz A (1981) Levels of dynorphin (1–13)-immunoreactivity in rat neurointermediate pituitaries are concomitantly altered with those of leucine enkephalin and vasopressin in response to various endocrine manipulations. Neuroendocrinology 33:333–339.

    Article  PubMed  Google Scholar 

  15. Höllt V, Haarmann I, Seizinger BR, Herz A (1982) Chronic haloperidol treatment increases the level of the in vitro translatable mRNA coding for the β-endorphin/ACTH precursor proopiomelanocortin in the pars intermedia of the rat pituitary. Endocrinology 110:1885–1891.

    Article  PubMed  Google Scholar 

  16. Höllt V, Haarmann I, Millan MJ, Herz A (1987) Prodynorphin gene expression is enhanced in the spinal cord of chronic arthritic rats. Neurosci Lett 73:80–94.

    Article  Google Scholar 

  17. Karras A, Kane J (1980) Naloxone reduces cigarette smoking. Life Sci 27:1541–1545.

    Article  CAS  PubMed  Google Scholar 

  18. Kellar KJ, Giblin BA, Lumpkin MD (1989) Regulation of brain nicotinic recognition sites and prolactin release by nicotine. In: Nordberg A, Fuxe K, Homstedt B, Sundwall A (eds) Progress in brain research. (vol 79) Elsevier Science Publishers BV, Amsterdam, pp 209–216.

    Google Scholar 

  19. Lichtensteiger W, Hefti F, Felix D, Huwyler T, Melamed E, Schlumpf M (1982) Stimulation of nigrostriatal dopamine neurones by nicotine. Neuropharmacology 21:963–968.

    Article  CAS  PubMed  Google Scholar 

  20. Marks MJ, Burch JB, Collins AC (1983) Effects of chronic nicotine infusion on tolerance development and nicotinic receptors. J Pharmacol Exp Ther 226:817–825.

    CAS  PubMed  Google Scholar 

  21. Morris BJ, Herz A, Höllt V (1989) Localization of striatal opioid gene expression and its modulation by mesostriatal dopamine pathway: an in situ hybridization study. J Mot Neurosci 1:9–18.

    Article  CAS  Google Scholar 

  22. Pomerleau OF, Fertig JB, Seyler LE, Jaffe J (1983) Neuroendocrine reactivity to nicotine in smokers. Psychopharmacology 81:61–67.

    Article  CAS  PubMed  Google Scholar 

  23. Rapier C, Lunt CG, Wonnacott S (1988) Stereoselective nicotine-induced release of dopamine from striatal synaptosomes: concentration dependence and repetetive stimulation. J Neurochem 50:1123–1130.

    Article  CAS  PubMed  Google Scholar 

  24. Sharp BM, Beyer HS (1986) Rapid desensitization of the acute stimulatory effects of nicotine on rat plasma adrenocorticotropin and prolactin. J Pharmacol Exp Ther 238:486–491.

    CAS  PubMed  Google Scholar 

  25. Sladek CD, Joynt RJ (1979) Cholinergic involvement in osmotic control of vasopressin release by the organ-cultured rat hypothalamo-neurohypophyseal system. Endocrinology 105:367–371.

    Article  CAS  PubMed  Google Scholar 

  26. Stalke J, Hader O, Hensen J, Bähr V, Scherer G, Oelkers W (1991) Nicotine infusion in man stimulates plasma-vasopressin, ACTH and cortisol in a dose dependent manner. In: Adlkofer F, Thurau K (eds) Effects of nicotine on biological systems. (Advances in Pharmacological Sciences) Birkhäuser, Basel, pp 339–343.

    Chapter  Google Scholar 

  27. Villanueva HF, Arezo S, Rosecrans JA (1991) Preliminary studies on the in vivo desensitization of central nicotinic receptors by (−)-nicotine. In: Adlkofer F, Thurau K (eds) Effects of nicotine on biological systems. (Advances in Pharmacological Sciences) Birkhäuser, Basel, pp 355–359.

    Chapter  Google Scholar 

  28. Viveros OH, Wilson SP, Chang KJ (1982) Regulation of synthesis and secretion of enkephalins and related peptides in adrenomedullary chromaffin cells and human pheochromocytoma. In: Costa E, Trabucchi M (eds) Regulatory peptides. Raven Press, New York, pp 217–224.

    Google Scholar 

  29. Watson SJ, Akil H, Fischli W, Goldstein A, Zimmermann E, Nilaver G, von Wimmersma Greidanus TB (1982) Dynorphin and vasopressin: common localization in magnocellular neurones. Science 216:85–87.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Physiologisches Institut, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 12, W-8000, München 2, Germany

    V. Höllt & G. Horn

Authors
  1. V. Höllt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. Horn
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Höllt, V., Horn, G. Effect of nicotine on mRNA levels encoding opioid peptides, vasopressin and α3 nicotinic receptor subunit in the rat. Clin Investig 70, 224–231 (1992). https://doi.org/10.1007/BF00184655

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00184655

Key words

Search

Navigation