Veterinary Research Communications

, Volume 9, Issue 1, pp 89–113 | Cite as

Central and local actions of opioids upon reticulo-ruminal motility in sheep

  • C. L. Maas
  • B. F. Leek
Research Articles


The effects of opioids and naloxone on cyclical forestomach motility were determined in anaesthetized and conscious sheep. To assess central or peripheral opioid actions, differential routes of administration were used. Possible dynamic effects along the innervating vagovagal reflex arc were investigated electrophysiologically at the cervical level of the vagus nerve. Further, direct influences on the smooth muscle were evaluatedin vitro on isolated longitudinal reticular strips. Additionally, the effects of some spasmogenic agents were studied for comparative purposes. In anaesthetized sheep, opioids depressed in an identical manner both the amplitude of spontaneous cyclical contractions and contractions evoked by electrical stimulation of the distal end of the cut cervical vagus. In conscious sheep, low doses of normorphine and loperamide inhibited frequency and amplitude centrally (20 μg/kg and 4 μg/kg via carotid artery respectively), whereas locally higher dose levels (200 μg/kg and 10 μg/kg via coeliac artery respectively) affected only the amplitude of cyclical contractions. Furthermore the opioid peptides Leu-, Met-enkephalin and [D-Ala2-Met5]-enkephalinamide preferentially depressed the amplitude of cyclical motility most efficiently if administrated via the coeliac artery. These results indicate the presence both of a central opioid action depressing frequency and amplitude and of a local opioid action depressing only the amplitude of cyclical reticulo-ruminal motility. Opioids did not alter the resting discharge of afferent tension units and similarly failed to modulate tone of reticular stripsin vitro, suggesting that the opioids act locally on the intramural neuronal plexus, possibly by diminishing the output of excitatory transmitter. Whether substance P could play a role as a vagal excitatory transmitter besides the classically implicated acetylcholine has been discussed. The central opioid mechanism is probably not situated within the gastric centres but elsewhere in the brain. Naloxone (≥ 100 μg/kg, jugular vein) stimulated the frequency of cyclical ruminal motility only in well-defined experimental conditions, probably via a central mechanism.


Naloxone Loperamide Excitatory Transmitter Opioid Action Cyclical Contraction 
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. Ambinder, R.F. and Schuster, M.M. (1979). Endorphins: new gut peptides with a familiar face. Gastroenterology 77:1132–1140.Google Scholar
  2. Barthó, L., Sebök, B. and Szolcsanyi, J. (1982). Indirect evidence for the inhibition of enteric substance P neurones by opiate agonists but not by capsaicin. Eur. J. Pharmac. 77:273–279.Google Scholar
  3. Burleigh, D., Galligan, J.J. and Burks, T.F. (1981). Subcutaneous morphine reduces intestinal propulsion in rats partly by a central action. Eur. J. Pharmac. 75:283–287.Google Scholar
  4. Cornford, E.M., Braun, L.D., Crane, P.D., and Oldendorf, W.H. (1978). Blood-brain barrier restriction of peptides and the low uptake of enkephalins. Endocrinology 103:1297–1303.Google Scholar
  5. Gamse, R., Lembeck, F. and Cuello, A.C. (1979). Substance P in the vagus nerve. Naunyn-Schmiedebergs Arch Pharmac. 306:37–44.Google Scholar
  6. Gintzler, A.R. and Scalisi, J.A. (1982). Effects of opioids on noncholinergic excitatory responses of the guinea-pig isolated ileum: inhibition of release of enteric substance P. Br. J. Pharmac. 75:199–205.Google Scholar
  7. Harding, R. and Leek, B.F. (1972). The effects of peripheral and central nervous influences on gastric centre neuronal activity in sheep. J. Physiol. (London) 225:309–338.Google Scholar
  8. Harthoorn, A.M. and Bligh, J. (1965). The use of a new oripavine derivative with potent morphine-like activity for the restraint of hoofed wild animals. Res. Vet. Sci. 6:290–299.Google Scholar
  9. Iggo, A. and Leek, B.F. (1967a). An electrophysiological study of single vagal efferent units associated with gastric movements in sheep. J. Physiol. (London) 191:177–204.Google Scholar
  10. Iggo, A. and Leek, B.F. (1967b). An electrophysiological study of some reticulo-ruminal and abomasal reflexes in sheep. J. Physiol. (London) 193:95–119.Google Scholar
  11. Jean-Blain, C., Borivin, R. and Bost, J. (1971). Digestibilité et rumination-effets de la morphine par voie cérebro-ventriculaire chez le mouton. Ann. Nutr. Alim. 25:121–138.Google Scholar
  12. Leek, B.F. (1967). An electrophysiological analysis of the reflex regulation of reticulo-ruminal movements. Thesis (Edinburgh).Google Scholar
  13. Leek, B.F. (1969). Reticulo-ruminal mechanoreceptors in sheep. J. Physiol. (London) 202:285–609.Google Scholar
  14. Leek, B.F. (1976). A simple and effective ruminal cannulation technique for sheep. J. Physiol. (London) 263:233–234P.Google Scholar
  15. Leek, B.F. and Harding, R.H. (1975). Sensory nervous receptors in the ruminant stomach and the reflex control of reticulo-ruminal motility. In: Digestion and metabolism in the ruminant (McDonald, I.W. and Warner, A.C.I., Ed.), pp. 60–76. The University of New England Publishing Unit, Armidale.Google Scholar
  16. Leek, B.F. and Van Miert, A.S.J.P.A.M. (1971). An analysis of the gastric stasis induced by pyrogen. The effects on intrinsic and extrinsic movements of the ruminant forestomach. Rendiconti Romani di Gastro-enterologia 3:163–167.Google Scholar
  17. Maas, C.L. (1982). Opiate antagonists stimulate ruminal motility of conscious goats. Eur. J. Pharmac. 77:71–74.Google Scholar
  18. Maas, C.L., Van Duin, C.T.M. and Van Miert, A.S.J.P.A.M. (1982). Modification by domperidone of dopamine- and apomorphine-induced inhibition of extrinsic ruminal contractions in goats. J. vet. Pharmacol. Ther. 5:191–196.Google Scholar
  19. Ohlsson, A.E., Fu, T.C., Jones, D., Martin, B.R. and Dewey, W.L. (1982). Distribution of radioactivity in the spinal cord after intracerebroventricular and intravenous injection of radiolabeled opioid peptides in mice. J. Pharmac. exp. Ther. 221: 362–367.Google Scholar
  20. Paton, W.D.M. (1957). The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum. Br. J. Pharmac. 11:119–127.Google Scholar
  21. Pert, C.B., Pert, A., Chang, J.-K. and Fong, B.T.W. (1976). [D-Ala2]-Met-Enkephalinamide: A potent, long-lasting synthetic pentapeptide analgesic. Science 194:330–332.Google Scholar
  22. Schulz, R., Wüster, M. and Herz, A. (1979). Centrally and peripherally mediated inhibition of intestinal motility by opioids. Naunyn-Schmiedebergs Arch. Pharmac. 308:255–260.Google Scholar
  23. Sellers, A.F. and Stevens, C.E. (1966). Motor functions of the ruminant forestomach. Physiol. Rev. 46:634–661.Google Scholar
  24. Stewart, J.J., Weisbrodt, N.W. and Burks, T.F. (1978). Central and peripheral actions of morphine on intestinal transit. J. Pharmac. exp. Ther. 205:547–555.Google Scholar
  25. Thurmon, J.C., Nelson, D.R. and Kumar, A. (1974). Etorphine and triflu promazine as immobilizing agents in the goat. J. Am. Vet. Med. Assoc. 165:168–171.Google Scholar
  26. Titchen D.A. (1968). Nervous control of motility of the forestomach of ruminants. In: Handbook of Physiology — section 6: Alimentary canal (Code, C.F. and Heidel, W., Ed.), pp. 2705–2724. American Physiological Soc., Washington.Google Scholar
  27. Uvnãs-Wallensten, K. (1978). Release of substance P-like immunoreactivity into the antral lumen of cats. Acta Physiol. Scand. 104:464–468.Google Scholar
  28. Van Miert, A.S.J.P.A.M. (1969). The effects of α- and β-sympathicomimetics on rumen motility and heart rate frequency in conscious goats. J. Pharm. Pharmac. 21:697–699.Google Scholar
  29. Van Miert, A.S.J.P.A.M. (1970). Motiliteitsremming van de netmaag en pens bij de kleine herkauwer tijdens de door bacterieel endotoxine (lipopolysaccharide) opgewekte koorts. Thesis (Utrecht).Google Scholar
  30. Van Miert, A.S.J.P.A.M., Van der Wal-Komproe, L.E. and Van Duin, C.T.M. (1977). Effects of antipyretic agents on fever and ruminal stasis induced by endotoxins in conscious goats. Archs int. Pharmacodyn. Ther. 225:39–50.Google Scholar
  31. Vaughan Williams, E.M. and Streeten, D.H.P. (1950). The action of morphine, pethidine, and amidone upon the intestinal motility of conscious dogs. Br. J. Pharmac. 5:584–603.Google Scholar
  32. Veenendaal, G.H., Woutersen-van Nijnanten, F.M.A. and Van Miert, A.S.J.P.A.M. (1982). Responses of goat ruminal musculature to substance P in vitro and in vivo. Vet. Res. Commun. 5:363–367.Google Scholar
  33. Von Euler, U.S. (1963). Substance P in subcellular particles in peripheral nerves. Ann. N.Y. Acad. Sci. 104:449–461.Google Scholar
  34. Waterfield, A.A., Smokcum, R.W.J., Hughes, J., Kosterlitz, H.W. and Henderson, G. (1977). In vitro pharmacology of the opiate peptides, enkephalins and endorphins. Eur. J. Pharmac. 43:107–116.Google Scholar
  35. Wood, J.D. (1981). Intrinsic neural control of intestinal motility. Ann. Rev. Physiol. 43:33–51.Google Scholar

Copyright information

© Elsevier Science Publishers B.V 1985

Authors and Affiliations

  • C. L. Maas
    • 1
  • B. F. Leek
    • 2
  1. 1.Institute of Veterinary Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary MedicineUtrecht UniversityUtrecht(The Netherlands)
  2. 2.Department of Veterinary Physiology and BiochemistryUniversity College DublinDublin 4(Ireland)

Personalised recommendations