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. 1989 Mar;96(3):739–745. doi: 10.1111/j.1476-5381.1989.tb11876.x

Effects of tetrodotoxin on relaxation of pig duodenal circular muscle induced by C-terminal fragments of cholecystokinin.

I Kimura 1, T Kondoh 1, M Kimura 1
PMCID: PMC1854384  PMID: 2541851

Abstract

1. The mechanisms by which cholecystokinin (CCK)-C-terminal peptides relax the isolated duodenal circular muscles of pigs were compared with mechanisms involving high potassium and electrical stimulation. 2. The relaxation (30%) induced by CCK-8 0.263 nM was completely and non-competitively blocked by tetrodotoxin (TTX) 0.313 microM, and was enhanced 2-2.5 times by mesaconitine 0.158 microM, tetraethylammonium (TEA) 0.597 mM and ouabain 0.136 microM. 3. The TTX sensitivity was greater for CCK-8 and CCK-6, than for CCK-5 and CCK-4. 4. High potassium (11.8-23.6 mM)-induced, or electrically stimulated (0.3-30 Hz) relaxation showed similar characteristics except that they were not antagonized by the CCK antagonist P3-I (168 microM). 5. Apamin (0.385-3.85 microM) enhanced relaxation induced by 10.6 mM K+, but did not affect relaxation induced by CCK-8. 6. These results indicate that: (1) CCK-8, K+, and transmural electrical stimulation relax duodenal circular muscles by releasing an endogenous inhibitory substance; (2) the latter two do not mediate the release of CCK; and (3) the mechanisms for relaxation by CCK-4 are different from those of CCK-8.

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Selected References

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  1. ARMSTRONG C. M., BINSTOCK L. ANOMALOUS RECTIFICATION IN THE SQUID GIANT AXON INJECTED WITH TETRAETHYLAMMONIUM CHLORIDE. J Gen Physiol. 1965 May;48:859–872. doi: 10.1085/jgp.48.5.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Behar J., Biancani P. Effect of cholecystokinin and the octapeptide of cholecystokinin on the feline sphincter of Oddi and gallbladder. Mechanisms of action. J Clin Invest. 1980 Dec;66(6):1231–1239. doi: 10.1172/JCI109974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Behar J., Biancani P. Effect of cholecystokinin-octapeptide on lower esophageal sphincter. Gastroenterology. 1977 Jul;73(1):57–61. [PubMed] [Google Scholar]
  4. Biancani P., Walsh J. H., Behar J. Vasoactive intestinal polypeptide. A neurotransmitter for lower esophageal sphincter relaxation. J Clin Invest. 1984 Apr;73(4):963–967. doi: 10.1172/JCI111320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bonaccorsi A., Hermsmeyer K., Smith C. B., Bohr D. F. Norepinephrine release in isolated arteries induced by K-free solution. Am J Physiol. 1977 Feb;232(2):H140–H145. doi: 10.1152/ajpheart.1977.232.2.H140. [DOI] [PubMed] [Google Scholar]
  6. Gillespie J. S., Tilmisany A. K. The action of tetraethyl-ammonium chloride on the response of the rat anococcygeus muscle to motor and inhibitory nerve stimulation and to some drugs. Br J Pharmacol. 1976 Sep;58(1):47–55. doi: 10.1111/j.1476-5381.1976.tb07692.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ishi T., Shimo Y. Potassium-induced relaxation of the rat anococcygeus muscle. Arch Int Pharmacodyn Ther. 1980 Jan;243(1):27–36. [PubMed] [Google Scholar]
  8. Ishii T., Shimo Y. Potassium-induced relaxations of the guinea-pig taenia coli. Arch Int Pharmacodyn Ther. 1979 May;239(1):36–44. [PubMed] [Google Scholar]
  9. Kao C. Y. Pharmacology of tetrodotoxin and saxitoxin. Fed Proc. 1972 May-Jun;31(3):1117–1123. [PubMed] [Google Scholar]
  10. Kimura I., Kimura M., Kimura M. Potassium induces relaxation and hyperpolarization of circular muscles but contraction of longitudinal muscles of pig duodenum. Br J Pharmacol. 1984 Sep;83(1):187–193. doi: 10.1111/j.1476-5381.1984.tb10134.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kimura I., Kimura M., Nakayama N., Kimura M. Relaxation and Ca-spike suppression in circular and longitudinal muscles of hog bile duct ampulla by CCK-C-terminal peptides. Arch Int Pharmacodyn Ther. 1983 Oct;265(2):320–334. [PubMed] [Google Scholar]
  12. Kimura I., Kondoh T., Kimura M. Proglumide peptides and CCK antagonistic action in hog duodenal circular muscle. Eur J Pharmacol. 1987 Feb 10;134(2):181–187. doi: 10.1016/0014-2999(87)90164-6. [DOI] [PubMed] [Google Scholar]
  13. Kirkpatrick C. T. Excitation and contraction in bovine tracheal smooth muscle. J Physiol. 1975 Jan;244(2):263–281. doi: 10.1113/jphysiol.1975.sp010796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Paton W. D., Vizi E. S., Zar M. A. The mechanism of acetylcholine release from parasympathetic nerves. J Physiol. 1971 Jul;215(3):819–848. doi: 10.1113/jphysiol.1971.sp009500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Reiner O. The role of the electrogenic sodium pump in the potassium relaxation of the rabbit ear artery. Naunyn Schmiedebergs Arch Pharmacol. 1978 Jul;303(3):213–220. doi: 10.1007/BF00498046. [DOI] [PubMed] [Google Scholar]
  16. Sakamoto Y., Tomita T. Depolarization produced by sodium removal in the circular muscle of the guinea-pig stomach. J Physiol. 1982 May;326:329–339. doi: 10.1113/jphysiol.1982.sp014196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Weir S. W., Weston A. H. Effect of apamin on responses to BRL 34915, nicorandil and other relaxants in the guinea-pig taenia caeci. Br J Pharmacol. 1986 May;88(1):113–120. doi: 10.1111/j.1476-5381.1986.tb09477.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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