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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1980;71(1):297–305. doi: 10.1111/j.1476-5381.1980.tb10939.x

Inhibitory actions of methionine-enkephalin and morphine on the cat carotid chemoreceptors.

D S McQueen, J A Ribeiro
PMCID: PMC2044409  PMID: 6781573

Abstract

1 The effects of intracarotid injections of methionine-enkephalin (Met-enkephalin) and morphine on chemoreceptor activity recorded from the peripheral end of a sectioned carotid sinus nerve have been studied in cats anaesthetized with pentobarbitone. 2 Met-enkephalin caused a rapid, powerful, inhibition of spontaneous chemoreceptor discharge, the intensity and duration of which was dose-dependent. 3 Morphine was a less potent inhibitor of spontaneous chemoreceptor discharge, and the inhibition it evoked was rather variable and tended to be biphasic. Low doses of morphine caused a slight increase in discharge. 4 Naloxone (0.2 mg i.c.) slightly increased spontaneous discharge, greatly reduced the chemo-inhibition caused by morphine, and reduced the inhibitory effect of Met-enkephalin. A higher dose of naloxone (0.8 mg) caused a substantial reduction of the Met-enkephalin effect. 5 Chemo-excitation evoked by intracarotid injections of acetylcholine, CO2-saturated Locke solution, and sodium cyanide were only slightly and somewhat variably reduced following injections of Met-enkephalin, whereas the inhibitory effect of dopamine was potentiated. Following morphine administration, response to acetylcholine and sodium cyanide were reduced slightly, whereas those to CO2 and dopamine were potentiated. 6 Responses to acetylcholine and CO2 were slightly potentiated during infusion of Met-enkephalin (50 micrograms/min, i.c.) and the response to sodium cyanide was slightly reduced. 7 It is concluded that naloxone-sensitive opiate receptors are present in the cat carotid body; when activated they cause inhibition of spontaneous chemoreceptor discharge. The physiological role of these receptors and the identity of any endogenous ligand remains to be established.

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Selected References

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  1. Arndt J. O., Freye E. Opiate antagonist reverses the cardiovascular effects of inhalation anaesthesia. Nature. 1979 Feb 1;277(5695):399–400. doi: 10.1038/277399a0. [DOI] [PubMed] [Google Scholar]
  2. Cuello A. C., McQueen D. S. Substance P: a carotid body peptide. Neurosci Lett. 1980 Apr;17(1-2):215–219. doi: 10.1016/0304-3940(80)90087-7. [DOI] [PubMed] [Google Scholar]
  3. Docherty R. J., McQueen D. S. Inhibitory action of dopamine on cat carotid chemoreceptors. J Physiol. 1978 Jun;279:425–436. doi: 10.1113/jphysiol.1978.sp012354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Duggan A. W., Hall J. G., Headley P. M. Enkephalins and dorsal horn neurones of the cat: effects on responses to noxious and innocuous skin stimuli. Br J Pharmacol. 1977 Nov;61(3):399–408. doi: 10.1111/j.1476-5381.1977.tb08432.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. EYZAGUIRRE C., LEWIN J. Effect of different oxygen tensions on the carotid body in vitro. J Physiol. 1961 Dec;159:238–250. doi: 10.1113/jphysiol.1961.sp006805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Eyzaguirre C., Zapata P. Pharmacology of pH effects on carotid body chemoreceptors in vitro. J Physiol. 1968 Apr;195(3):557–588. doi: 10.1113/jphysiol.1968.sp008474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fürst Z., Foldes F. F., Knoll J. The influence of naloxone on barbiturate anesthesia and toxicity in the rat. Life Sci. 1977 Mar 15;20(6):921–926. doi: 10.1016/0024-3205(77)90276-4. [DOI] [PubMed] [Google Scholar]
  8. Guerrero-Munoz F., Cerreta K. V., Guerrero M. L., Way E. L. Effect of morphine on synaptosomal Ca++ uptake. J Pharmacol Exp Ther. 1979 Apr;209(1):132–136. [PubMed] [Google Scholar]
  9. Guerrero-Munoz F., de Lourdes Guerrero M., Way E. L., Li C. H. Effect of beta-endorphin on calcium uptake in the brain. Science. 1979 Oct 5;206(4414):89–91. doi: 10.1126/science.39340. [DOI] [PubMed] [Google Scholar]
  10. Henderson G., Hughes J., Kosterlitz H. W. The effects of morphine on the release of noradrenaline from the cat isolated nictitating membrane and the guinea-pig ileum myenteric plexus-longitudinal muscle preparation. Br J Pharmacol. 1975 Apr;53(4):505–512. doi: 10.1111/j.1476-5381.1975.tb07387.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jessell T. M., Iversen L. L. Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature. 1977 Aug 11;268(5620):549–551. doi: 10.1038/268549a0. [DOI] [PubMed] [Google Scholar]
  12. Katz B., Miledi R. The role of calcium in neuromuscular facilitation. J Physiol. 1968 Mar;195(2):481–492. doi: 10.1113/jphysiol.1968.sp008469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. LANDGREN S., LILJESTRAND G., ZOTTERMAN Y. The effect of certain autonomic drugs on the action potentials of the sinus nerve. Acta Physiol Scand. 1952 Sep 10;26(2-3):264–290. doi: 10.1111/j.1748-1716.1952.tb00909.x. [DOI] [PubMed] [Google Scholar]
  15. Loh H. H., Brase D. A., Sampath-Khanna S., Mar J. B., Way E. L., Li C. H. beta-Endorphin in vitro inhibition of striatal dopamine release. Nature. 1976 Dec 9;264(5586):567–568. doi: 10.1038/264567a0. [DOI] [PubMed] [Google Scholar]
  16. Lord J. A., Waterfield A. A., Hughes J., Kosterlitz H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature. 1977 Jun 9;267(5611):495–499. doi: 10.1038/267495a0. [DOI] [PubMed] [Google Scholar]
  17. McQueen D. S. A quantitative study of the effects of cholinergic drugs on carotid chemoreceptors in the cat. J Physiol. 1977 Dec;273(2):515–532. doi: 10.1113/jphysiol.1977.sp012107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McQueen D. S. Effects of substance P on carotid chemoreceptor activity in the cat. J Physiol. 1980 May;302:31–47. doi: 10.1113/jphysiol.1980.sp013228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mudge A. W., Leeman S. E., Fischbach G. D. Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration. Proc Natl Acad Sci U S A. 1979 Jan;76(1):526–530. doi: 10.1073/pnas.76.1.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. North R. A. Opiates, opioid peptides and single neurones. Life Sci. 1979 Apr 23;24(17):1527–1545. doi: 10.1016/0024-3205(79)90014-6. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Ribeiro J. A. ATP; related nucleotides and adenosine on neurotransmission. Life Sci. 1978 Apr 24;22(16):1373–1380. doi: 10.1016/0024-3205(78)90630-6. [DOI] [PubMed] [Google Scholar]
  23. Ribeiro J. A., Sá-Almeida A. M., Namorado J. M. Adenosine and adenosine triphosphate decrease 45Ca uptake by synaptosomes stimulated by potassium. Biochem Pharmacol. 1979 Apr 15;28(8):1297–1300. doi: 10.1016/0006-2952(79)90428-3. [DOI] [PubMed] [Google Scholar]
  24. SZERB J. C. The effect of morphine on the adrenergic nerves of the isolated guinea-pig jejunum. Br J Pharmacol Chemother. 1961 Feb;16:23–31. doi: 10.1111/j.1476-5381.1961.tb00294.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sawynok J., Jhamandas K. H. Inhibition of acetylcholine release from cholinergic nerves by adenosine, adenine nucleotides and morphine: antagonism by theophylline. J Pharmacol Exp Ther. 1976 May;197(2):379–390. [PubMed] [Google Scholar]
  26. Sawynok J., Pinsky C., LaBella F. S. On the specificity of naloxone as an opiate antagonist. Life Sci. 1979 Nov 5;25(19):1621–1632. doi: 10.1016/0024-3205(79)90403-x. [DOI] [PubMed] [Google Scholar]
  27. Snyder S. H., Childers S. R. Opiate receptors and opioid peptides. Annu Rev Neurosci. 1979;2:35–64. doi: 10.1146/annurev.ne.02.030179.000343. [DOI] [PubMed] [Google Scholar]
  28. Stone T. W., Perkins M. N. Is adenosine the mediator of opiate action on neuronal firing rate? Nature. 1979 Sep 20;281(5728):227–228. doi: 10.1038/281227a0. [DOI] [PubMed] [Google Scholar]

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