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Tachykinins Stimulate Release of Peptide Hormones (Glucagon-Like Peptide-1) and Paracrine (Somatostatin) and Neurotransmitter (Vasoactive Intestinal Polypeptide) from Porcine Ileum Through NK-1 Receptors

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Abstract

The effects of infusion of the two tachykinins,substance P (SP) and neurokinin A (NKA), and ofcapsaicin on the release of glucagon-like peptide-1(GLP-1), somatostatin, and vasoactive intestinalpolypeptide (VIP) were studied in isolated, vascularlyperfused ileal segments. SP (10-8 M) stimulated GLP-1,somatostatin, and VIP release to 141.8 ± 6.6% (N= 18), 230.3 ± 38.7% (N = 21), and 359.7 ±60.5% (N = 22) of basal output, respectively. NKA(10-8 M) only stimulated VIP release (to181.2 ± 16.7% of basal release, N = 22). Theeffects of SP and NKA were blocked by the NK-1 receptorantagonist CP96345 (10-6 M). Infusion of atropine(10-6 M) had no effect on the SP-inducedGLP-1 release, but partly inhibited the effect of SP onsomatostatin and VIP release, and the effect of NKA onVIP release. Capsaicin infusions (10-5 M) significantlystimulated both GLP-1, somatostatin, and VIP release to111.1 ± 4.5% (N = 9), 138.0 ± 15.8% (N =9) and 208.3 ± 63.8% (N = 8) of basal release,respectively. Simultaneous addition of receptor antagonists to all threetachykinin receptors (CP96345, SR48968, and SR142801,all at 10-6 M) significantly inhibited theeffect of capsaicin on VIP release, whereas the releaseof GLP-1 and somatostatin was unaffected. Weconclude that tachykinins potently stimulate the releaseof GLP-1, somatostatin, and VIP in the porcine ileum viaNK-1 receptors. The effect on somatostatin and VIP is partly mediated via cholinergic neurons.Sensory neurons releasing tachykinins could be involvedin the regulation of VIPergic neurons.

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REFERENCES

  1. Schmidt P, Poulsen SS, Rasmussen TN, Bersani M, Holst JJ: Substance P and neurokinin A are codistributed and colocalized in the porcine gastrointestinal tract. Peptides 12:963–973, 1991

    Google Scholar 

  2. Holzer P, Holzer-Petsche U: Tachykinins in the gut. Part 1. Expression, release and motor function. Pharmacol Ther 73:173–217, 1997

    Google Scholar 

  3. Holzer P, Holzer-Pe tsche U: Tachykinins in the gut. Part 2. Roles in neural excitation, secretion and inflammation. Pharmacol Ther 73:219–263, 1997

    Google Scholar 

  4. Hermann-Rinke C, Voge A, Hess M, Gô ke B: Regulation of glucagon-like peptide 1 secretion from rat ileum by neurotransmitters and peptides. J Endocrinol 147:25–31, 1995

    Google Scholar 

  5. Ørskov C, Holst JJ, Knuthsen S, Baldissera FGA, Poulsen SS, Nielsen OV: Glucagon-like peptides GLP-1 and GLP-2, predicted products of the glucagon gene, are secreted separate ly from the pig small intestine but not pancreas. Endocrinology 119:1467–1475, 1986

    Google Scholar 

  6. Dumoulin V, Dakka T, Plaisancie P, Cheyvaille JA, Cuber JC: Regulation of glucagon-like peptide-1 (7–36) amide, peptide YY, and neurotensin secretion by neurotransmitters and gut hormones in the isolated vascularly perfused rat ileum. Endocrinology 136:5182–5188, 1995

    Google Scholar 

  7. Furness JB, Costa M: The Enteric Ne rvous System. Edinburgh, Churchill Livingstone, 1987

    Google Scholar 

  8. Skak-Nielsen T, Holst JJ, Baldissera FGA, Poulsen SS: Localization in the gastrointe stinal tract of immunore active prosomatostatin. Regul Pept 19:183–195, 1987

    Google Scholar 

  9. Baldissera FGA, Nielsen OV, Holst JJ: The intestinal mucosa preferentially releases somatostatin-28 in pigs. Regul Pept 11:251–262, 1985

    Google Scholar 

  10. Schmidt P, Rasmussen TN, Holst JJ: Release of immunore active somatostatin, vasoactive intestinal polypeptide (VIP), and galanin during propulsive complexes in isolated ileum. Peptides 14:215–220, 1993

    Google Scholar 

  11. Baldissera FGA, Holst JJ, Jensen SL, Krarup T: Distribution and molecular forms of peptides containing somatostatin immunode te rminants in extracts from the entire gastrointestinal tract of man and pig. Biochim Biophys Acta 838:132–143, 1985

    Google Scholar 

  12. Messel T, Harling H, Poulsen SS, Bersani M, Holst JJ: Extrinsic control of release of galanin and VIP from intrinsic nerves of isolated, perfused, porcine ileum. Regul Pept 38:179–198, 1992

    Google Scholar 

  13. Harling H, Messell T, Poulsen SS, Rasmussen TN, Holst JJ: Galanin and vasoactive intestinal polypeptide: Coexistence and core lease from the vascularly perfused ileum during distension and chemical stimulation of the mucosa. Digestion 50:61–71, 1991

    Google Scholar 

  14. Manaka H, Manaka Y, Kostolanska F, Fox JET, Daniel EE: Release of VIP and substance P from isolated perfused canine ileum. Am J Physiol 20:G182-G190, 1989

    Google Scholar 

  15. Watson EG, Fox-Threlkeld JET, Daniel EE: Tachykininmediated increase in motility acts independently of vasoactive inte stinal polypeptide release in the canine ileum. Can J Physiol Pharmacol 72:109–112, 1992

    Google Scholar 

  16. Brunsson I, Fahrenkrug J, Jodal M, Sjöqvist A, Lundgren O: Substance P effects on blood flow, fluid transport and vasoactive intestinal polypeptide release in the feline small intestine. J Physiol (London) 483:727–734, 1995

    Google Scholar 

  17. Holst JJ. Isolated organs as replacement for ve rtebrate animals. In Handbook of Laboratory Animal Science. P Svendsen, J Hau (eds). Boca Raton, Florida, CRC Press, 1994, pp 397–408

    Google Scholar 

  18. Snider RM, Constantine JW, Lowe III JA, Longo KP, Lebel WS, Woody HA, Drozda SE, Desai MC, Vinick FJ, Spencer RW, Hess H-J: A potent nonpeptide antagonist of the substance P (NK1) receptor. Science 251:435–437, 1991

    Google Scholar 

  19. Guard S, Boyle SJ, Tang K-W, Watling KJ, McKnight AT, Woodruff GN: The interaction of NK1 receptor antagonist CP-96,345 with L-type **calcium channels and its functional consequences. Br J Pharmacol 110:385–391, 1993

    Google Scholar 

  20. Pothoulakis C, Castagiuolo I, LaMont JT, Jaffer A, O'Keane JC, Snider RM, Leeman SE: CP-96,345, a substance P antagonist, inhibits rat intestinal responses to Clostridium difficile toxin A but not cholera toxin. Proc Natl Acad Sci USA 91:947–951, 1994

    Google Scholar 

  21. Schmidt AW, McLean S, Heym J: The substance P receptor antagonist CP-96,345 interacts with Ca2+ channels. Eur J Pharmacol 215:351–352, 1992

    Google Scholar 

  22. Wang Z-Y, Hå kanson R: (± )-CP-96,345, a se lective tachykinin NK1 receptor antagonist, has non-specific actions on neurotransmission. Br J Pharmacol 107:762–765, 1992

    Google Scholar 

  23. Advenier C, Rouissi N, Nguyen QT, Amonds-Alt X, Breliere J-C, Neliat G, Naline E, Regoli D: Neurokinin A (NK2) receptor revisited with SR 48968, a potent non-peptide antagonist. Biochem Biophys Res Comm 184:1418–1424, 1992

    Google Scholar 

  24. Emond-Alt X, Bichon D, Ducoux JP, Heaulme M, Miloux B, Poncelet M, Proietto V, Van Broeck D, Vilain P, Neliat G, Soubrié P, Le Fur G, Breliè re JC: SR 142801, the first potent non-peptide antagonist of the tachykinin NK3 receptor. Life Sci 56:PL27-PL32, 1994

    Google Scholar 

  25. Fahrenkrug J, Schaffalitzsky de Muckadell OB: Radioimmunoassay of vasoactive intestinal polypeptide (VIP) in plasma. J Lab Clin Med 89:1379–1388, 1977

    Google Scholar 

  26. Hilsted L, Holst JJ: On the accuracy of radioimmunological determination of somatostatin in plasma. Regul Pept 4:13–31, 1982

    Google Scholar 

  27. Ørskov C, Rabenhø j L, Wettergren A, Kofod H, Holst JJ: Tissue and plasma concentration of amidated and glycine-extended glucagon-like peptide I in humans. Diabetes 43:535–539, 1994

    Google Scholar 

  28. Schmidt P, Rasmussen TN, Holst JJ: Nervous control of release of substance P and neurokinin A from the isolated perfused porcine ileum. J Auton Nerv Syst 38:85–96, 1992

    Google Scholar 

  29. Chiba T, Yamada T: Gut somatostatin. In Gut Peptides. JH Walsh, GJ Dockrey (eds). Comparative Endocrinology. Luciano Martini (series ed). New York, Raven Press, 1994, pp 123–145

    Google Scholar 

  30. Schmidt P, Poulsen SP, Hilsted L, Rasmussen TR, Holst JJ: Tachykinins mediate vagal inhibition of gastrin secretion in pigs. Gastroenterol 111:925–935, 1996

    Google Scholar 

  31. Fox JE, Daniel EE: Substance P: A potent inhibitor of canine small intestine in vivo. Am J Physiol 250:G21-G27, 1986

    Google Scholar 

  32. Daniel EE, Parrish MB, Watson EG, Fox-Threlkeld JE, Regoli D, Rainsford KD: The tachykinin re ceptors inducing contractile responses of canine ileum circular muscle. Am J Physiol 268:G161-G170, 1995

    Google Scholar 

  33. Fox-Threlkeld JE, Manaka H, Manaka Y, Cipris S, Daniel EE: Stimulation of circular muscle motility of the isolated perfused canine ileum: Re lationship to VIP output. Peptides 12:1039–1045, 1991

    Google Scholar 

  34. Schmidt PT, Holst JJ: Use of antagonists to define tachykininergic control of intestinal motility in pigs. Peptides 18:373–379, 1997

    Google Scholar 

  35. Thorbø ll JE, Bindslev N, Tindholdt TT, Schmidt P, Skadhauge E: Tachykinins mediate changes in ion transport in porcine jejunum through the release of prostaglandins and neurotransmitters. Regul Pept 16:105–111, 1998

    Google Scholar 

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Authors
  1. Peter Thelin Schmidt
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  2. Lars Fledelius Rickelt
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  3. Jens Juul Holst
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Schmidt, P.T., Rickelt, L.F. & Holst, J.J. Tachykinins Stimulate Release of Peptide Hormones (Glucagon-Like Peptide-1) and Paracrine (Somatostatin) and Neurotransmitter (Vasoactive Intestinal Polypeptide) from Porcine Ileum Through NK-1 Receptors. Dig Dis Sci 44, 1273–1281 (1999). https://doi.org/10.1023/A:1026610626068

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