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. 1983 Dec;80(4):645–653. doi: 10.1111/j.1476-5381.1983.tb10054.x

Pharmacological characterization of the inhibitory effects of neurotensin on the rabbit ileum myenteric plexus preparation.

J P Huidobro-Toro, K Yoshimura
PMCID: PMC2045053  PMID: 6152827

Abstract

Neurotensin in picomolar concentrations caused a concentration-related inhibition of the spontaneous contractile activity of the longitudinal muscle from the rabbit isolated ileum. Neurotensin was approximately 100 times more potent than adrenaline and about 10000 times as active as adenosine triphosphate (ATP) in producing similar relaxations. The neurotensin-induced inhibitory effect did not follow activation of adrenoceptors or P1-purinoceptors since the effect of the neuropeptide was not antagonized by a combination of phentolamine plus (-)-propranolol, nor by pretreatment with theophylline. Tetrodotoxin did not reduce the potency of neurotensin in relaxing the rabbit ileum, suggesting that the neurotensin-induced inhibition is not neuronally mediated. The inhibitory responses of neurotensin were blocked non-competitively by apamin. The inhibitory effect of neurotensin was short-lived with the subsequent development of tachyphylaxis, which was not crossed to the inhibitory action of adrenaline or ATP. Similarly, when tachyphylaxis to adrenaline or to ATP was established, the inhibitory action of neurotensin was unaffected. Desensitization was characterized by a gradual shift of the neuropeptide concentration-response curve to the right and downwards. Preincubation of rabbit ileum strips with 10 nM dynorphin (1-13) significantly increased the inhibitory action of neurotensin.

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Selected References

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  1. Banks B. E., Brown C., Burgess G. M., Burnstock G., Claret M., Cocks T. M., Jenkinson D. H. Apamin blocks certain neurotransmitter-induced increases in potassium permeability. Nature. 1979 Nov 22;282(5737):415–417. doi: 10.1038/282415a0. [DOI] [PubMed] [Google Scholar]
  2. Brown C. M., Burnstock G. Evidence in support of the P1/P2 purinoceptor hypothesis in the guinea-pig taenia coli. Br J Pharmacol. 1981 Jul;73(3):617–624. doi: 10.1111/j.1476-5381.1981.tb16796.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chow E. H., Marshall J. M. Effects of catecholamines on circular and longitudinal uterine muscle of the rat. Eur J Pharmacol. 1981 Dec 3;76(2-3):157–165. doi: 10.1016/0014-2999(81)90497-0. [DOI] [PubMed] [Google Scholar]
  4. Goldstein A., Fischli W., Lowney L. I., Hunkapiller M., Hood L. Porcine pituitary dynorphin: complete amino acid sequence of the biologically active heptadecapeptide. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7219–7223. doi: 10.1073/pnas.78.11.7219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Goldstein A., Tachibana S., Lowney L. I., Hunkapiller M., Hood L. Dynorphin-(1-13), an extraordinarily potent opioid peptide. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6666–6670. doi: 10.1073/pnas.76.12.6666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Huidobro-Toro J. P., Chelala C. A., Bahouth S., Nodar R., Musacchio J. M. Fading and tachyphylaxis to the contractile effects of substance P in the guinea-pig ileum. Eur J Pharmacol. 1982 Jun 16;81(1):21–34. doi: 10.1016/0014-2999(82)90597-0. [DOI] [PubMed] [Google Scholar]
  7. Huidobro-Toro J. P., Foree B. Dual agonist-antagonist effects of 5-hydroxytryptamine (5-HT) in the guinea pig ileum: evidence for a selective receptor desensitization effect. Eur J Pharmacol. 1980 Feb;61(4):335–345. doi: 10.1016/0014-2999(80)90072-2. [DOI] [PubMed] [Google Scholar]
  8. Huidobro-Toro J. P., Way E. L. Possible modulatory role of dynorphin on the excitation by neurotensin on the guinea pig myenteric plexus. Neurosci Lett. 1982 Jun 30;30(3):309–314. doi: 10.1016/0304-3940(82)90418-9. [DOI] [PubMed] [Google Scholar]
  9. Kachur J. F., Miller R. J., Field M., Rivier J. Neurohumoral control of ileal electrolyte transport. II. Neurotensin and substance P. J Pharmacol Exp Ther. 1982 Mar;220(3):456–463. [PubMed] [Google Scholar]
  10. Kitabgi P. Effects of neurotensin on intestinal smooth muscle: application to the study of structure-activity relationships. Ann N Y Acad Sci. 1982;400:37–55. doi: 10.1111/j.1749-6632.1982.tb31559.x. [DOI] [PubMed] [Google Scholar]
  11. Kitabgi P., Freychet P. Effects of neurotensin on isolated intestinal smooth muscles. Eur J Pharmacol. 1978 Aug 15;50(4):349–357. doi: 10.1016/0014-2999(78)90140-1. [DOI] [PubMed] [Google Scholar]
  12. Kitabgi P., Vincent J. P. Neurotensin is a potent inhibitor of guinea-pig colon contractile activity. Eur J Pharmacol. 1981 Sep 24;74(4):311–318. doi: 10.1016/0014-2999(81)90050-9. [DOI] [PubMed] [Google Scholar]
  13. Leeman S. E., Carraway R. E. Neurotensin: discovery, isolation, characterization, synthesis and possible physiological roles. Ann N Y Acad Sci. 1982;400:1–16. doi: 10.1111/j.1749-6632.1982.tb31557.x. [DOI] [PubMed] [Google Scholar]
  14. Luttinger D., Frye G. D., Nemeroff C. B., Prange A. J., Jr The effects of neurotensin, beta-endorphin, and bombesin on ethanol-induced behaviors in mice. Psychopharmacology (Berl) 1983;79(4):357–363. doi: 10.1007/BF00433418. [DOI] [PubMed] [Google Scholar]
  15. Mashford M. L., Nilsson G., Rökaeus A., Rosell S. The effect of food ingestion on circulating neurotensin-like immunoreactivity (NTLI) in the human. Acta Physiol Scand. 1978 Oct;104(2):244–246. doi: 10.1111/j.1748-1716.1978.tb06275.x. [DOI] [PubMed] [Google Scholar]
  16. Polak J. M., Sullivan S. N., Bloom S. R., Buchan A. M., Facer P., Brown M. R., Pearse A. G. Specific localisation of neurotensin to the N cell in human intestine by radioimmunoassay and immunocytochemistry. Nature. 1977 Nov 10;270(5633):183–184. doi: 10.1038/270183a0. [DOI] [PubMed] [Google Scholar]
  17. Quirion R., Regoli D., Rioux F., St-Pierre S. The stimulatory effects of neurotensin and related peptides in rat stomach strips and guinea-pig atria. Br J Pharmacol. 1980 Jan;68(1):83–91. doi: 10.1111/j.1476-5381.1980.tb10702.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rosell S., Rökaeus A. The effect of ingestion of amino acids, glucose and fat on circulating neurotensin-like immunoreactivity (NTLI) in man. Acta Physiol Scand. 1979 Nov;107(3):263–267. doi: 10.1111/j.1748-1716.1979.tb06472.x. [DOI] [PubMed] [Google Scholar]
  19. Tachibana S., Araki K., Ohya S., Yoshida S. Isolation and structure of dynorphin, an opioid peptide, from porcine duodenum. Nature. 1982 Jan 28;295(5847):339–340. doi: 10.1038/295339a0. [DOI] [PubMed] [Google Scholar]
  20. Williams J. T., Katayama Y., North R. A. The action of neurotensin on single myenteric neurones. Eur J Pharmacol. 1979 Nov 16;59(3-4):181–186. doi: 10.1016/0014-2999(79)90280-2. [DOI] [PubMed] [Google Scholar]
  21. Yoshimura K., Huidobro-Toro J. P., Lee N. M., Löh H. H., Way E. L. Kappa opioid properties of dynorphin and its peptide fragments on the guinea-pig Ileum. J Pharmacol Exp Ther. 1982 Jul;222(1):71–79. [PubMed] [Google Scholar]
  22. Zhu Y. X., Huidobro-Toro J. P., Lee N. M., Loh H. H., Way E. L. Interaction of dynorphin with neurotensin on the guinea pig ileum myenteric plexus. Life Sci. 1982 Oct 18;31(16-17):1825–1828. doi: 10.1016/0024-3205(82)90220-x. [DOI] [PubMed] [Google Scholar]

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