Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Jun;81(6):1920–1924. doi: 10.1172/JCI113539

Vasoactive intestinal polypeptide mediates cholecystokinin-induced relaxation of the sphincter of Oddi.

J W Wiley 1, T M O'Dorisio 1, C Owyang 1
PMCID: PMC442644  PMID: 3384954

Abstract

This study evaluates the hypothesis that cholecystokinin (CCK) relaxes the sphincter of Oddi via vasoactive intestinal polypeptide (VIP). Isolated canine sphincter of Oddi were suspended in organ baths under standard conditions. Responses to cholecystokinin octapeptide (CCK-8) and VIP were recorded on a pen recorder via an isometric transducer. 10(-11)-10(-7) M CCK-8 and 4 X 10(-11)-5 X 10(-7) M VIP generated dose-related sphincter of Oddi relaxation, which was unaffected by atropine, propranolol, and phentolamine. The effect of CCK-8 was antagonized by dibutyryl cGMP (Bt2 cGMP) (10(-3) M), the VIP-antagonist (N-Ac-Tyr1, D-Phe2)-growth hormone-releasing factor-(1-29)-NH2, and abolished by tetrodotoxin. In contrast, VIP's relaxing action was tetrodotoxin insensitive. 10(-11)-10(-7) M CCK-8 stimulated dose-dependent release of VIP (0.5-2.2 fm/ml.mg tissue), which was not inhibited by atropine, propranolol, and phentolamine, but was antagonized by 10(-3) M Bt2 cGMP and tetrodotoxin. In addition CCK-8 and VIP generated dose-related (10(-10)-10(-7) M) increases in sphincter of Oddi cAMP levels that were not affected by atropine, propranolol, and phentolamine. Furthermore, 10(-5)-10(-2) M 8-bromo-cAMP caused dose-dependent relaxation of the sphincter of Oddi. In separate studies, a 2-h incubation in physiological solution containing 12 parts/1,000 of rabbit VIP antiserum antagonized sphincter relaxation caused by 4 nM CCK-8 and 6 nM VIP. The antiserum also significantly decreased the sphincter of Oddi cAMP level stimulated by 4 nM CCK-8 by 48 +/- 15%. These studies demonstrate that CCK-8 relaxes the canine sphincter of Oddi via a noncholinergic, nonadrenergic neural pathway involving VIP. The intracellular mechanism mediating CCK/VIP relaxation involves generation of cAMP.

Full text

PDF
1924

Images in this article

1922Image
on p.1922

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alumets J., Schaffalitzky de Muckadell O., Fahrenkrug J., Sundler F., Håkanson R., Uddman R. A rich VIP nerve supply is characteristic of sphincters. Nature. 1979 Jul 12;280(5718):155–156. doi: 10.1038/280155a0. [DOI] [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. Neural control of the sphincter of Oddi. Physiologic role of enkephalins on the regulation of basal sphincter of Oddi motor activity in the cat. Gastroenterology. 1984 Jan;86(1):134–141. [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. Biancani P., Walsh J., Behar J. Vasoactive intestinal peptide: a neurotransmitter for relaxation of the rabbit internal anal sphincter. Gastroenterology. 1985 Oct;89(4):867–874. doi: 10.1016/0016-5085(85)90585-2. [DOI] [PubMed] [Google Scholar]
  6. Bitar K. N., Makhlouf G. M. Relaxation of isolated gastric smooth muscle cells by vasoactive intestinal peptide. Science. 1982 Apr 30;216(4545):531–533. doi: 10.1126/science.6176025. [DOI] [PubMed] [Google Scholar]
  7. EICHHORN E. P., Jr, BOYDEN E. A. The choledochoduodenal junction in the dog; a restudy of Oddi's sphincter. Am J Anat. 1955 Nov;97(3):431–459. doi: 10.1002/aja.1000970305. [DOI] [PubMed] [Google Scholar]
  8. Fahrenkrug J., Haglund U., Jodal M., Lundgren O., Olbe L., de Muckadell O. B. Nervous release of vasoactive intestinal polypeptide in the gastrointestinal tract of cats: possible physiological implications. J Physiol. 1978 Nov;284:291–305. doi: 10.1113/jphysiol.1978.sp012541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gaginella T. S., O'Dorisio T. M., Hubel K. A. Release of vasoactive intestinal polypeptide by electrical field stimulation of rabbit ileum. Regul Pept. 1981 Jun;2(3):165–174. doi: 10.1016/0167-0115(81)90010-0. [DOI] [PubMed] [Google Scholar]
  10. Geenen J. E., Hogan W. J., Dodds W. J., Stewart E. T., Arndorfer R. C. Intraluminal pressure recording from the human sphincter of Oddi. Gastroenterology. 1980 Feb;78(2):317–324. [PubMed] [Google Scholar]
  11. Honeyman T., Merriam P., Fay F. S. The effects of isoproterenol on adenosine cyclic 3', 5'- monophosphate and contractility in isolated smooth muscle cells. Mol Pharmacol. 1978 Jan;14(1):86–98. [PubMed] [Google Scholar]
  12. Morgan K. G., Schmalz P. F., Go V. L., Szurszewski J. H. Electrical and mechanical effects of molecular variants of CCK on antral smooth muscle. Am J Physiol. 1978 Sep;235(3):E324–E329. doi: 10.1152/ajpendo.1978.235.3.E324. [DOI] [PubMed] [Google Scholar]
  13. Persson C. G., Ekman M. Effect of morphine, cholecystokinin and sympathomimetics on the sphincter of Oddi and intramural pressure in cat duodenum. Scand J Gastroenterol. 1972;7(4):345–351. doi: 10.3109/00365527209180753. [DOI] [PubMed] [Google Scholar]
  14. Persson C. G. Resistance to flow through the pancreatic duct by the isolated cat sphincter of oddi. Experientia. 1972 Mar 15;28(3):276–278. doi: 10.1007/BF01928686. [DOI] [PubMed] [Google Scholar]
  15. Scheid C. R., Honeyman T. W., Fay F. S. Mechanism of beta-adrenergic relaxation of smooth muscle. Nature. 1979 Jan 4;277(5691):32–36. doi: 10.1038/277032a0. [DOI] [PubMed] [Google Scholar]
  16. Toouli J., Hogan W. J., Geenen J. E., Dodds W. J., Arndorfer R. C. Action of cholecystokinin-octapeptide on sphincter of Oddi basal pressure and phasic wave activity in humans. Surgery. 1982 Sep;92(3):497–503. [PubMed] [Google Scholar]
  17. Vaitukaitis J. L., Lee C. Y., Ebersole E. R., Lerario A. C. New evidence for an acute role of protein kinase in hCG action. Endocrinology. 1975 Jul;97(1):215–222. doi: 10.1210/endo-97-1-215. [DOI] [PubMed] [Google Scholar]
  18. Waelbroeck M., Robberecht P., Coy D. H., Camus J. C., De Neef P., Christophe J. Interaction of growth hormone-releasing factor (GRF) and 14 GRF analogs with vasoactive intestinal peptide (VIP) receptors of rat pancreas. Discovery of (N-Ac-Tyr1,D-Phe2)-GRF(1-29)-NH2 as a VIP antagonist. Endocrinology. 1985 Jun;116(6):2643–2649. doi: 10.1210/endo-116-6-2643. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES