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. 1980 Mar;68(3):381–392. doi: 10.1111/j.1476-5381.1980.tb14551.x

Acute effects of morphine and opioid peptides on the motility and responses of rat colon to electrical stimulation.

M G Gillan, D Pollock
PMCID: PMC2044203  PMID: 7052334

Abstract

1 Morphine and leucine- and methionine-enkephalins inhibited the contractile response of the pithed rat colon to electrical stimulation of the spinal motor outflows and inhibited motor responses of the isolated colon to field stimulation. 2 Morphine and the opioid peptides also had an excitatory action in the colon. In the pithed rat, opiates caused regular fluctuations in intracolonic pressure and in the isolated colon, caused regular waves of contraction. This excitatory response was produced by low concentrations of the enkephalins (2 X 10(-8) M, 2 X 10(-9) M), was stereospecific and was antagonized by naloxone. 3 Opiate-induced contractions in the isolated colon were inhibited by catecholamines, adenine nucleotides and by phosphodiesterase inhibitors. These contractions were unaffected by ergotamine and tolazoline, or by propranolol. 4 The excitatory action of opiates in the isolated colon was not antagonized and usually was potentiated by atropine, (+)-tubocurarine and hexamethonium. In the absence of opiates, these drugs also produced similar waves of contraction, which were unaffected by naloxone. 5 Opiate-induced contractions occurred in colon rendered unresponsive to 5-hydroxytryptamine (5-HT) and these contractions were potentiated by the 5-HT antagonist, lysergic acid diethylamide, which, when administered alone, caused similar contractions. The 5-HT antagonist, cyproheptadine, inhibited opiate-induced contractions but was non-specific, since it also inhibited responses of the colon to carbachol and KC1. 6 Opiate-induced contractions were unaffected by procaine and were potentiated by tetrodotoxin. Both of these drugs, when administered alone, produced waves of contractions, which were similar to those produced by opiates but were unaffected by naloxone. 7 Contractions produced in the isolated colon either by opiates, atropine or (+)-tubocurarine, or any combination of these drugs, were inhibited by field stimulation applied at the peak of a wave of contraction. This inhibitory response to field stimulation occurred at low frequencies of stimulation (less than 10 Hz), and persisted in colon from rats pretreated with reserpine to deplete, or 6-hydroxydopamine to destroy, adrenergic nerve endings. It was unaffected by guanethidine but abolished by tetrodotoxin. 8 The implications of these results are considered and it is concluded that the excitatory action of opiates in the rat colon is probably not mediated by the release of acetylcholine or 5-HT but instead, may be due either to a direct action on smooth muscle or to a presynaptic inhibitory action at a ganglionic site in a non-adrenergic inhibitory mechanism, which normally suppresses myogenic activity.

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Selected References

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  1. BURN J. H., RAND M. J. The relation of circulating noradrenaline to the effect of sympathetic stimulation. J Physiol. 1960 Feb;150:295–305. doi: 10.1113/jphysiol.1960.sp006388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett M. R. Rebound excitation of the smooth muscle cells of the guinea-pig taenia coli after stimulation of intramural inhibitory nerves. J Physiol. 1966 Jul;185(1):124–131. doi: 10.1113/jphysiol.1966.sp007975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bortoff A., Muller R. Stimulation of intestinal smooth muscle by atropine, procaine, and tetrodotoxin. Am J Physiol. 1975 Dec;229(6):1609–1613. doi: 10.1152/ajplegacy.1975.229.6.1609. [DOI] [PubMed] [Google Scholar]
  4. Burks T. F. Acute effects of morphine on rat intestinal motility. Eur J Pharmacol. 1976 Dec;40(2):279–283. doi: 10.1016/0014-2999(76)90063-7. [DOI] [PubMed] [Google Scholar]
  5. Burks T. F., Long J. P. Release of intestinal 5-hydroxytryptamine by morphine and related agents. J Pharmacol Exp Ther. 1967 May;156(2):267–276. [PubMed] [Google Scholar]
  6. Burks T. F. Mediation by 5-hydroxytryptamine of morphine stimulant actions in dog intestine. J Pharmacol Exp Ther. 1973 Jun;185(3):530–539. [PubMed] [Google Scholar]
  7. Burnstock G., Cocks T., Paddle B., Staszewska-Barczak J. Evidence that prostaglandin is responsible for the 'rebound contraction' following stimulation of non-adrenergic, non-cholinergic ('purinergic') inhibitory nerves. Eur J Pharmacol. 1975 Apr;31(2):360–362. doi: 10.1016/0014-2999(75)90060-6. [DOI] [PubMed] [Google Scholar]
  8. Dingledine R., Goldstein A., Kendig J. Effects of narcotic opiates and serotonin on the electrical behavior of neurons in the guinea pig myenteric plexus. Life Sci. 1974 Jun 1;14(11):2299–2309. doi: 10.1016/0024-3205(74)90111-8. [DOI] [PubMed] [Google Scholar]
  9. Ehrenpreis S., Sato T., Takayanagi I., Comaty J. E., Takagi K. Mechanism of morphine block of electrical activity in ganglia of Auerbach's plexus. Eur J Pharmacol. 1976 Dec;40(2):303–309. doi: 10.1016/0014-2999(76)90067-4. [DOI] [PubMed] [Google Scholar]
  10. Elde R., Hökfelt T., Johansson O., Terenius L. Immunohistochemical studies using antibodies to leucine-enkephalin: initial observations on the nervous system of the rat. Neuroscience. 1976 Aug;1(4):349–351. doi: 10.1016/0306-4522(76)90063-4. [DOI] [PubMed] [Google Scholar]
  11. Furness J. B., Costa M. The adrenergic innervation of the gastrointestinal tract. Ergeb Physiol. 1974;69(0):2–51. [PubMed] [Google Scholar]
  12. Furness J. B. Secondary excitation of intestinal smooth muscle. Br J Pharmacol. 1971 Feb;41(2):213–226. doi: 10.1111/j.1476-5381.1971.tb08023.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gillan M. G., Pollock D. Investigation of the effects of drugs on morphine-induced contractions of the isolated colon of the rat [proceedings]. Br J Pharmacol. 1976 Jul;57(3):444P–445P. [PMC free article] [PubMed] [Google Scholar]
  14. Gillespie J. S., Kirpekar S. M. The histological localization of noradrenaline in the cat spleen. J Physiol. 1966 Nov;187(1):69–79. doi: 10.1113/jphysiol.1966.sp008076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gillespie J. S., Maclaren A., Pollock D. A method of stimulating different segments of the autonomic outflow from the spinal column to various organs in the pithed cat and rat. Br J Pharmacol. 1970 Oct;40(2):257–267. doi: 10.1111/j.1476-5381.1970.tb09919.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hambrook J. M., Morgan B. A., Rance M. J., Smith C. F. Mode of deactivation of the enkephalins by rat and human plasma and rat brain homogenates. Nature. 1976 Aug 26;262(5571):782–783. doi: 10.1038/262782a0. [DOI] [PubMed] [Google Scholar]
  17. Hughes J. Enkephalin and drug dependence. Br J Addict Alcohol Other Drugs. 1976 Sep;71(3):199–209. [PubMed] [Google Scholar]
  18. Hughes J. Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Res. 1975 May 2;88(2):295–308. doi: 10.1016/0006-8993(75)90391-1. [DOI] [PubMed] [Google Scholar]
  19. Hughes J., Kosterlitz H. W., Smith T. W. The distribution of methionine-enkephalin and leucine-enkephalin in the brain and peripheral tissues. Br J Pharmacol. 1977 Dec;61(4):639–647. doi: 10.1111/j.1476-5381.1977.tb07557.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kosterlitz H. W., Hughes J. Some thoughts on the significance of enkephalin, the endogenous ligand. Life Sci. 1975 Jul 1;17(1):91–96. doi: 10.1016/0024-3205(75)90243-x. [DOI] [PubMed] [Google Scholar]
  21. NORBERG K. A. ADRENERGIC INNERVATION OF THE INTESTINAL WALL STUDIED BY FLUORESCENCE MICROSCOPY. Int J Neuropharmacol. 1964 Sep;3:379–382. doi: 10.1016/0028-3908(64)90067-x. [DOI] [PubMed] [Google Scholar]
  22. Narahashi T. Mechanism of action of tetrodotoxin and saxitoxin on excitable membranes. Fed Proc. 1972 May-Jun;31(3):1124–1132. [PubMed] [Google Scholar]
  23. PATON W. D. The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea-pig ileum. Br J Pharmacol Chemother. 1957 Mar;12(1):119–127. doi: 10.1111/j.1476-5381.1957.tb01373.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Persson C. G. Excitatory effect of tetrodotoxin on an isolated smooth muscle organ. J Pharm Pharmacol. 1971 Dec;23(12):986–987. doi: 10.1111/j.2042-7158.1971.tb09914.x. [DOI] [PubMed] [Google Scholar]
  25. Shimo Y., Ishii T. Effects of morphine on non-adrenergic inhibitory responses of the guinea-pig taenia coli. J Pharm Pharmacol. 1978 Sep;30(9):596–597. doi: 10.1111/j.2042-7158.1978.tb13337.x. [DOI] [PubMed] [Google Scholar]
  26. VAUGHAN WILLIAMS E. M. The mode of action of drugs upon intestinal motility. Pharmacol Rev. 1954 Jun;6(2):159–190. [PubMed] [Google Scholar]
  27. Vohra M. M. An analysis of the contractile responses of the rat vas deferens to xylocaine (lidocaine) and procaine. Eur J Pharmacol. 1970 Jan;9(1):14–20. doi: 10.1016/0014-2999(70)90314-6. [DOI] [PubMed] [Google Scholar]
  28. Wood J. D. Excitation of intestinal muscle by atropine, tetrodotoxin, and xylocaine. Am J Physiol. 1972 Jan;222(1):118–125. doi: 10.1152/ajplegacy.1972.222.1.118. [DOI] [PubMed] [Google Scholar]
  29. Wood J. D., Rose B. A., Jackson M. H. Effects of nicotine on rebound excitation of guinea-pig small intestine. J Pharmacol Exp Ther. 1976 Jan;196(1):71–79. [PubMed] [Google Scholar]

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