Skip to main content
SpringerLink
Log in

Functional Neurochemical Evidence for the Presence of Presynaptic Nicotinic Acetylcholine Receptors at the Terminal Region of Myenteric Motoneurons: A Study with Epibatidine

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

The aim of this study was to verify the presence of presynaptic nicotinic acetylcholine receptors (nAChRs) at the terminals of myenteric motoneurons using a potent and highly selective nicotinic agonist, epibatidine. We examined contraction, and release of [3H]ACh on a guinea-pig longitudinal muscle strip preparation. First, we compared the ability of epibatidine and nicotine to induce isometric contraction and found epibatidine (EC50 = 23.1 nM) to be 300-fold more potent than nicotine (EC50 = 7.09 μM). The release and contraction induced by 30 nM epibatidine were inhibited by the nicotinic antagonist mecamylamine (3 μM) and the Na1-channel blocker TTX (1 μM), indicating that the effects are mediated via nAChRs and are fully dependent on the propagation of action potentials. Atropine (0.1 μM) significantly increased the [3H]ACh release but could not block contraction suggesting that a substantial part of the response develops via a noncholinergic mechanism. Epibatidine at a higher concentration (300 nM) induced contraction, which was only partly (45%) inhibited by TTX (1 μM). The TTX-resistant contraction, however, was completely blocked by mecamylamine (3 μM). Our data provide functional neurochemical evidence for the existence of presynaptic nAChRs at myenteric motoneuron terminals and suggest that these receptors can be activated only/by a higher concentration of agonists.

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

REFERENCES

  1. Torocsik, A., Oberfrank, F., Sershen, H., Lajtha, A., Nemesy, K., and Vizi, E. S. 1991. Characterization of somatodendritic neuronal nicotinic receptors located on the myenteric plexus. Eur. J. Pharmacol. 202:297–302.

    PubMed  Google Scholar 

  2. Vizi, E. S., Sershen, H., Balla, A., Mike, A., Windisch, K., Juranyi, Z., and Lajtha, A. 1995. Neurochemical evidence of heterogeneity of presynaptic and somatodendritic nicotinic acetylcholine receptors. Ann. N. Y. Acad. Sci. 757:84–99.

    PubMed  Google Scholar 

  3. Galligan, J. J. 1999. Nerve terminal nicotinic cholinergic receptors on excitatory motoneurons in the myenteric plexus of guinea pig intestine. J. Pharmacol. Exp. Ther. 291:92–98.

    PubMed  Google Scholar 

  4. Ehlert, F. J., Sawyer, G. W., and Esqueda, E. E. 1999. Contractile role of M2 and M3 muscarinic receptors in gastrointestinal smooth muscle. Life Sci. 64:387–394.

    PubMed  Google Scholar 

  5. Vizi, E. S. 1979. Presynaptic modulation of neurochemical transmission. Prog. Neurobiol. 12:181–290.

    PubMed  Google Scholar 

  6. Paton, W. D. and Vizi, E. S. 1969. The inhibitory action of nor-adrenaline and adrenaline on acetylcholine output by guinea pig ileum longitudinal muscle strip. Br. J. Pharmacol. 35:10–28.

    PubMed  Google Scholar 

  7. Paton, W. D., Vizi, E. S., and Zar, M. A. 1971. The mechanism of acetylcholine release from parasympathetic nerves. J. Physiol. 215:819–848.

    PubMed  Google Scholar 

  8. Schneider, D. A., Perrone, M., and Galligan, J. J. 2000. Nicotinic acetylcholine receptors at sites of neurotransmitter release to the guinea pig intestinal circular muscle. J. Pharmacol. Exp. Ther. 294:363–369.

    PubMed  Google Scholar 

  9. Niebler, M. and Trendelenburg, U. 1990. Mechanisms of the release of 3H-noradrenaline by dimethylphenylpiperazinium (DMPP) in the rat vas deferens. Naunyn Schmiedebergs Arch. Pharmacol. 341:43–49.

    PubMed  Google Scholar 

  10. Kiss, J. P., Windisch, K., Balla, A., Sershen, H., and Lajtha, A. 1997. Dual effect of DMPP on the resting release of nor-adrenaline from rat hippocampal slices. Brain Res. Bull. 43: 257–262.

    PubMed  Google Scholar 

  11. Kiss, J. P., Windisch, K., De Oliveira, K., Hennings, E. C., Mike, A., and Szasz, B. K. 2001. Differential effect of nicotinic agonists on the [3H]norepinephrine release from rat hippocampal slices. Neurochem. Res. 26:943–950.

    PubMed  Google Scholar 

  12. Arqueros, L., Naquira, D., and Zunino, E. 1978. Nicotine-induced release of catecholamines from rat hippocampus and striatum. Biochem. Pharmacol. 27:2667–2674.

    PubMed  Google Scholar 

  13. Bonhaus, D. W., Bley, K. R., Broka, C. A., Fontana, D. J., Leung, E., Lewis, R., Shieh, A., and Wong, E. H. 1995. Characterization of the electrophysiological, biochemical and behavioral actions of epibatidine. J. Pharmacol. Exp. Ther. 272: 1199–1203.

    PubMed  Google Scholar 

  14. Gerzanich, V., Peng, X., Wang, F., Wells, G., Anand, R., Fletcher, S., and Lindstrom, J. 1995. Comparative pharmacology of epibatidine: A potent agonist for neuronal nicotinic acetylcholine receptors. Mol. Pharmacol. 48:774–782.

    PubMed  Google Scholar 

  15. Lembeck, F. 1999. Epibatidine: High potency and broad spectrum activity on neuronal and neuromuscular nicotinic acetylcholine receptors. Naunyn Schmiedebergs Arch. Pharmacol. 359:378–385.

    PubMed  Google Scholar 

  16. Kirchgessner, A. L. and Liu, M. T. 1998. Immunohistochemical localization of nicotinic acetylcholine receptors in the guinea pig bowel and pancreas. J. Comp. Neurol. 390:497–514.

    PubMed  Google Scholar 

  17. Spande, T. F., Garraffo, H. M., Yeh, H. J., Pu, Q. L., Pannell, L. K., and Daly, J. W. 1992. A new class of alkaloids from a dendrobatid poison frog: A structure for alkaloid 251F. J. Nat. Prod. 55:707–722.

    PubMed  Google Scholar 

  18. Bannon, A. W., Decker, M. W., Holladay, M. W., Curzon, P., Donnelly-Roberts, D., Puttfarcken, P. S., Bitner, R. S., Diaz, A., Dickenson, A. H., Porsolt, R. D., Williams, M., and Arneric, S. P. 1998. Broad-spectrum, non-opioid analgesic activity by selective modulation of neuronal nicotinic acetylcholine receptors. Science 279:77–81.

    PubMed  Google Scholar 

  19. Donnelly-Roberts, D. L., Puttfarcken, P. S., Kuntzweiler, T. A., Briggs, C. A., Anderson, D. J., Campbell, J. E., Piattoni-Kaplan, M., McKenna, D. G., Wasicak, J. T., Holladay, M. W., Williams, M., and Arneric, S. P. 1998. ABT-594 [(R)-5-(2-azetidinyl-methoxy)-2-chloropyridine]: A novel, orally effective analgesic acting via neuronal nicotinic acetylcholine receptors: I. In vitro characterization. J. Pharmacol. Exp. Ther. 285:777–786.

    PubMed  Google Scholar 

  20. Qian, C., Li, T., Shen, T. Y., Libertine-Garahan, L., Eckman, J., Biftu, T., and Ip, S. 1993. Epibatidine is a nicotinic analgesic. Eur. J. Pharmacol. 250:R13–R14.

    PubMed  Google Scholar 

  21. Alkondon, M. and Albuquerque, E. X. 1995. Diversity of nicotinic acetylcholine receptors in rat hippocampal neurons: III. Agonist actions of the novel alkaloid epibatidine and analysis of type II current. J. Pharmacol. Exp. Ther. 274:771–782.

    PubMed  Google Scholar 

  22. Kadlec, O., Seferna, I., Sevcik, J., Somogyi, G. T., and Vizi, E. S. 1990. The topographical basis of cholinergic transmission in guinea pig ileum myenteric plexus. Neuroscience 36:793–802.

    PubMed  Google Scholar 

  23. Somogyi, G. T. and Vizi, E. S. 1988. Evidence that cholinergic axon terminals are equipped with both muscarinic and adenosine receptors. Brain Res. Bull. 21:575–579.

    PubMed  Google Scholar 

  24. Wonnacott, S. 1997. Presynaptic nicotinic ACh receptors. Trends Neurosci. 20:92–98.

    PubMed  Google Scholar 

  25. Vizi, E. S. and Lendvai, B. 1999. Modulatory role of presynap-tic nicotinic receptors in synaptic and non-synaptic chemical communication in the central nervous system. Brain Res. Brain Res. Rev. 30:219–235.

    PubMed  Google Scholar 

  26. Vizi, E. S. 2000. Role of high-affinity receptors and membrane transporters in nonsynaptic communication and drug action in the central nervous system. Pharmacol. Rev. 52:63–90.

    PubMed  Google Scholar 

  27. Coulie, B., Camilleri, M., Bharucha, A. E., Sandborn, W. J., and Burton, D. 2001. Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects. Aliment Pharmacol. Ther. 15: 653–663.

    PubMed  Google Scholar 

  28. Green, J. T., McKirdy, H. C., Rhodes, J., Thomas, G. A., and Evans, B. K. 1999. Intra-luminal nicotine reduces smooth muscle tone and contractile activity in the distal large bowel. Eur. J. Gastroenterol. Hepatol. 11:1299–1304.

    PubMed  Google Scholar 

  29. Meier, R., Beglinger, C., Dederding, J. P., Meyer-Wyss, B., Fumagalli, M., Rowedder, A., Turberg, Y., and Brignoli, R. 1995. Influence of age, gender, hormonal status and smoking habits on colonic transit time. Neurogastroenterol. Motil. 7:235–238.

    PubMed  Google Scholar 

  30. Rausch, T., Beglinger, C., Alam, N., Gyr, K., and Meier, R. 1998. Effect of transdermal application of nicotine on colonic transit in healthy nonsmoking volunteers. Neurogastroenterol. Motil. 10:263–270.

    PubMed  Google Scholar 

  31. Somogyi, G. T., Zernova G. V., Yoshiyama, M., Rocha, J. N., Smith C. P., and Groat, W. C. 2003. Change in muscarinic modulation of transmitter release in the rat urinary bladder after spinal cord injury. Neurochem. Int. In press.

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1450, Budapest, P.O. Box 67, Hungary

    P. Mandl, J. P. Kiss & E. S. Vizi

Authors
  1. P. Mandl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. P. Kiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. S. Vizi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. S. Vizi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mandl, P., Kiss, J.P. & Vizi, E.S. Functional Neurochemical Evidence for the Presence of Presynaptic Nicotinic Acetylcholine Receptors at the Terminal Region of Myenteric Motoneurons: A Study with Epibatidine. Neurochem Res 28, 407–412 (2003). https://doi.org/10.1023/A:1022884231313

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022884231313

Search

Navigation