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. 1994 Jan;111(1):288–294. doi: 10.1111/j.1476-5381.1994.tb14058.x

Stimulating action of KW-5139 (Leu13-motilin) on gastrointestinal motility in the rabbit.

T Kitazawa 1, S Ichikawa 1, T Yokoyama 1, A Ishii 1, K Shuto 1
PMCID: PMC1910044  PMID: 8012708

Abstract

1. The gastrointestinal motor stimulating action of the motilin analogue, KW-5139 (Leu13-motilin), was investigated both in the anaesthetized rabbit and in rabbit isolated smooth muscle tissues. 2. KW-5139 (0.3-10 micrograms kg-1, i.v.) produced motor stimulating actions in the gastric antrum, ileum and descending colon, the excitatory responses of which were initiated at the same time but declined with different time courses. The rank order of the excitatory response was: descending colon > or = gastric antrum >> ileum. 3. Atropine (1-3 mg kg-1, i.v.) or naloxone (1 mg kg-1, i.v.) completely suppressed the excitatory response to KW-5139 in the gastric antrum, but only partially attenuated that in the descending colon. This suggests that the mechanism of the excitatory response is different in the gastric antrum and the descending colon, and that cholinergic neural pathway is involved in the response of the gastric antrum. 4. KW-5139 (0.1 nM-1 microM) caused concentration-dependent contractions of the gastric antrum, duodenum, jejunum, ileum and the descending colon in vitro. In the rabbit intestine, the contractile response to KW-5139 was strongest in the duodenum and weakest in the ileum. 5. The contractile response to KW-5139 in the intestinal segments were not affected by tetrodotoxin, but were decreased by verapamil, or pretreatment with a high concentration of porcine motilin, confirming the involvement of motilin receptors in the response to KW-5139. 6. The present results suggest that the rabbit is a suitable species for the investigation of motilin on gut motility, because of the high responsiveness of the descending colon as well as the upper gastrointestinal tract.

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Selected References

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  1. Adachi H., Toda N., Hayashi S., Noguchi M., Suzuki T., Torizuka K., Yajima H., Koyama K. Mechanism of the excitatory action of motilin on isolated rabbit intestine. Gastroenterology. 1981 Apr;80(4):783–788. [PubMed] [Google Scholar]
  2. Banfield D. K., MacGillivray R. T., Brown J. C., McIntosh C. H. The isolation and characterization of rabbit motilin precursor cDNA. Biochim Biophys Acta. 1992 Jul 15;1131(3):341–344. doi: 10.1016/0167-4781(92)90038-2. [DOI] [PubMed] [Google Scholar]
  3. Bickel M., Belz U. Motilin and a synthetic enkephalin induce colonic motor complexes (CMC) in the conscious dog. Peptides. 1988 May-Jun;9(3):501–507. doi: 10.1016/0196-9781(88)90155-6. [DOI] [PubMed] [Google Scholar]
  4. Bormans V., Peeters T. L., Vantrappen G. Motilin receptors in rabbit stomach and small intestine. Regul Pept. 1986 Sep;15(2):143–153. doi: 10.1016/0167-0115(86)90084-4. [DOI] [PubMed] [Google Scholar]
  5. Brown J. C., Cook M. A., Dryburgh J. R. Motilin, a gastric motor activity stimulating polypeptide: the complete amino acid sequence. Can J Biochem. 1973 May;51(5):533–537. doi: 10.1139/o73-066. [DOI] [PubMed] [Google Scholar]
  6. Brown J. C., Mutt V., Dryburgh J. R. The further purification of motilin, a gastric motor activity stimulating polypeptide from the mucosa of the small intestine of hogs. Can J Physiol Pharmacol. 1971 May;49(5):399–405. doi: 10.1139/y71-047. [DOI] [PubMed] [Google Scholar]
  7. Depoortere I., Peeters T. L., Vantrappen G. Motilin receptors of the rabbit colon. Peptides. 1991 Jan-Feb;12(1):89–94. doi: 10.1016/0196-9781(91)90172-l. [DOI] [PubMed] [Google Scholar]
  8. Fox-Threlkeld J. E., Manaka H., Manaka Y., Cipris S., Woskowska Z., Daniel E. E. Mechanism of noncholinergic excitation of canine ileal circular muscle by motilin. Peptides. 1991 Sep-Oct;12(5):1047–1050. doi: 10.1016/0196-9781(91)90058-w. [DOI] [PubMed] [Google Scholar]
  9. Fox J. E., Daniel E. E., Jury J., Fox A. E., Collins S. M. Sites and mechanisms of action of neuropeptides on canine gastric motility differ in vivo and in vitro. Life Sci. 1983 Aug 29;33(9):817–825. doi: 10.1016/0024-3205(83)90619-7. [DOI] [PubMed] [Google Scholar]
  10. Fox J. E., Daniel E. E., Jury J., Robotham H. The mechanism of motilin excitation of the canine small intestine. Life Sci. 1984 Mar 5;34(10):1001–1006. doi: 10.1016/0024-3205(84)90305-9. [DOI] [PubMed] [Google Scholar]
  11. Hasler W. L., Heldsinger A., Chung O. Y. Erythromycin contracts rabbit colon myocytes via occupation of motilin receptors. Am J Physiol. 1992 Jan;262(1 Pt 1):G50–G55. doi: 10.1152/ajpgi.1992.262.1.G50. [DOI] [PubMed] [Google Scholar]
  12. Inatomi N., Satoh H., Maki Y., Hashimoto N., Itoh Z., Omura S. An erythromycin derivative, EM-523, induces motilin-like gastrointestinal motility in dogs. J Pharmacol Exp Ther. 1989 Nov;251(2):707–712. [PubMed] [Google Scholar]
  13. Itoh Z., Honda R., Hiwatashi K., Takeuchi S., Aizawa I., Takayanagi R., Couch E. F. Motilin-induced mechanical activity in the canine alimentary tract. Scand J Gastroenterol Suppl. 1976;39:93–110. [PubMed] [Google Scholar]
  14. Itoh Z., Mizumoto A., Iwanaga Y., Yoshida N., Torii K., Wakabayashi K. Involvement of 5-hydroxytryptamine 3 receptors in regulation of interdigestive gastric contractions by motilin in the dog. Gastroenterology. 1991 Apr;100(4):901–908. doi: 10.1016/0016-5085(91)90262-j. [DOI] [PubMed] [Google Scholar]
  15. Janssens J., Vantrappen G., Peeters T. L. The activity front of the migrating motor complex of the human stomach but not of the small intestine is motilin-dependent. Regul Pept. 1983 Aug;6(4):363–369. doi: 10.1016/0167-0115(83)90265-3. [DOI] [PubMed] [Google Scholar]
  16. Kitazawa T., Ishii A., Taniyama K. The Leu13-motilin (KW-5139)-evoked release of acetylcholine from enteric neurones in the rabbit duodenum. Br J Pharmacol. 1993 May;109(1):94–99. doi: 10.1111/j.1476-5381.1993.tb13536.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Koelbel C. B., Mayer E. A., Reeve J. R., Jr, Snape W. J., Jr, Patel A., Ho F. J. Involvement of substance P in noncholinergic excitation of rabbit colonic muscle. Am J Physiol. 1989 Jan;256(1 Pt 1):G246–G253. doi: 10.1152/ajpgi.1989.256.1.G246. [DOI] [PubMed] [Google Scholar]
  18. Lee K. Y., Chang T. M., Chey W. Y. Effect of rabbit antimotilin serum on myoelectric activity and plasma motilin concentration in fasting dog. Am J Physiol. 1983 Oct;245(4):G547–G553. doi: 10.1152/ajpgi.1983.245.4.G547. [DOI] [PubMed] [Google Scholar]
  19. Lüdtke F. E., Müller H., Golenhofen K. Direct effects of motilin on isolated smooth muscle from various regions of the human stomach. Pflugers Arch. 1989 Sep;414(5):558–563. doi: 10.1007/BF00580991. [DOI] [PubMed] [Google Scholar]
  20. Matsumoto T., Sarna S. K., Condon R. E., Cowles V. E., Frantzides C. Differential sensitivities of morphine and motilin to initiate migrating motor complex in isolated intestinal segments. Regeneration of intrinsic nerves. Gastroenterology. 1986 Jan;90(1):61–67. doi: 10.1016/0016-5085(86)90075-2. [DOI] [PubMed] [Google Scholar]
  21. Poitras P., Lahaie R. G., St-Pierre S., Trudel L. Comparative stimulation of motilin duodenal receptor by porcine or canine motilin. Gastroenterology. 1987 Mar;92(3):658–662. doi: 10.1016/0016-5085(87)90014-x. [DOI] [PubMed] [Google Scholar]
  22. Satoh T., Inatomi N., Satoh H., Marui S., Itoh Z., Omura S. EM-523, an erythromycin derivative, and motilin show similar contractile activity in isolated rabbit intestine. J Pharmacol Exp Ther. 1990 Sep;254(3):940–944. [PubMed] [Google Scholar]
  23. Segawa T., Nakano M., Kai Y., Kawatani H., Yajima H. Effect of synthetic motilin and related polypeptides on contraction of gastrointestinal smooth muscle. J Pharm Pharmacol. 1976 Aug;28(8):650–651. doi: 10.1111/j.2042-7158.1976.tb02822.x. [DOI] [PubMed] [Google Scholar]
  24. Vogel L. B., Brown J. C. Characterization of immunoreactive motilin from the rat small intestine. Can J Physiol Pharmacol. 1990 Aug;68(8):1124–1130. doi: 10.1139/y90-168. [DOI] [PubMed] [Google Scholar]
  25. Wingate D. L., Ruppin H., Green W. E., Thompson H. H., Domschke W., Wünsch E., Demling L., Ritchie H. D. Motilin-induced electrical activity in the canine gastrointestinal tract. Scand J Gastroenterol Suppl. 1976;39:111–118. [PubMed] [Google Scholar]

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