Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1991 Aug;439:89–102. doi: 10.1113/jphysiol.1991.sp018658

The role of cholecystokinin in ganglionic transmission in the guinea-pig gall-bladder.

G M Mawe 1
PMCID: PMC1180100  PMID: 1654421

Abstract

1. The effects of cholecystokinin (CCK) on intact guinea-pig gall-bladder ganglia were investigated with intracellular, single-electrode current- and voltage-clamp recording techniques. 2. Cholecystokinin octapeptide (CCK-8; 0.01-100 nM) increased the amplitude of the fast excitatory postsynaptic potential (EPSP) that was evoked by stimulation of interganglionic fibre tracts. In most cases, neurones that exhibited subthreshold EPSPs in normal Krebs solution fired action potentials in the presence of CCK-8. In a low Ca2+/high Mg2+ solution, CCK-8 caused a 3-fold increase in the amplitude of fast EPSPs. 3. The amplitude of the evoked excitatory postsynaptic current (EPSC) was increased by CCK-8 (0.01-100 nM) in a concentration-dependent manner. The effect was maximal at 1.0 nM. 4. Cholecystokinin octapeptide caused a 3-fold increase in the quantal content of the EPSP in a low Ca2+/high Mg2+ solution, but had no effect on the quantal size. 5. The specific CCK-A receptor antagonist, MK-329 (formerly L-364,718; 1.0 nM), reversibly blocked the facilitatory effect of CCK-8 on ganglionic transmission. However, the specific CCK-B receptor antagonist, L-365,260 (10 nM), did not alter the presynaptic facilitatory effect of CCK-8. 6. The response of gall-bladder neurones to exogenously applied ACh was not modified by CCK-8. 7. Application of CCK-8, by superfusion (0.001-100 nM) or by pressure microejection (100 microM), had no effect on the membrane potential, membrane conductance, action potential, or threshold of gall-bladder neurones. 8. Immunohistochemistry was employed to determine whether the actions of CCK could be elicited by release of the peptide from nerve terminals within the ganglionated plexus of the gall-bladder. Immunoreactivity for CCK was not detected in the ganglionated plexus of the gall-bladder, but CCK immunoreactivity was plentiful in control preparations of intestinal myenteric and submucosal plexuses. 9. These results show that CCK has a presynaptic facilitatory effect on fast synaptic transmission in guinea-pig gall-bladder ganglia, and that this effect is mediated by presynaptic CCK-A receptors. Furthermore, it appears that such an effect would normally occur in response to hormonal CCK, rather than CCK that is released from nerve terminals.

Full text

PDF
89

Images in this article

96Fig. 6
on p.96

Selected References

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

  1. Amer M. S., Becvar W. E. A sensitive in-vitro method for the assay of cholecystokinin. J Endocrinol. 1969 Apr;43(4):637–642. doi: 10.1677/joe.0.0430637. [DOI] [PubMed] [Google Scholar]
  2. Amer M. S. Studies with cholecystokinin in vitro. 3. Mechanism of the effect on the isolated rabbit gall bladder strips. J Pharmacol Exp Ther. 1972 Dec;183(3):527–534. [PubMed] [Google Scholar]
  3. 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]
  4. Behar J., Biancani P. Pharmacologic characterization of excitatory and inhibitory cholecystokinin receptors of the cat gallbladder and sphincter of Oddi. Gastroenterology. 1987 Mar;92(3):764–770. doi: 10.1016/0016-5085(87)90030-8. [DOI] [PubMed] [Google Scholar]
  5. Chang R. S., Lotti V. J. Biochemical and pharmacological characterization of an extremely potent and selective nonpeptide cholecystokinin antagonist. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4923–4926. doi: 10.1073/pnas.83.13.4923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DEL CASTILLO J., KATZ B. Quantal components of the end-plate potential. J Physiol. 1954 Jun 28;124(3):560–573. doi: 10.1113/jphysiol.1954.sp005129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DEL CASTILLO J., KATZ B. The effect of magnesium on the activity of motor nerve endings. J Physiol. 1954 Jun 28;124(3):553–559. doi: 10.1113/jphysiol.1954.sp005128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Eysselein V. E., Deveney C. W., Sankaran H., Reeve J. R., Jr, Walsh J. H. Biological activity of canine intestinal cholecystokinin-58. Am J Physiol. 1983 Aug;245(2):G313–G320. doi: 10.1152/ajpgi.1983.245.2.G313. [DOI] [PubMed] [Google Scholar]
  9. Fried G. M., Ogden W. D., Greeley G., Thompson J. C. Correlation of release and actions of cholecystokinin in dogs before and after vagotomy. Surgery. 1983 Jun;93(6):786–791. [PubMed] [Google Scholar]
  10. Hanyu N., Dodds W. J., Layman R. D., Hogan W. J., Chey W. Y., Takahashi I. Mechanism of cholecystokinin-induced contraction of the opossum gallbladder. Gastroenterology. 1990 May;98(5 Pt 1):1299–1306. doi: 10.1016/0016-5085(90)90348-5. [DOI] [PubMed] [Google Scholar]
  11. Hanyu N., Dodds W. J., Layman R. D., Hogan W. J. Cholecystokinin-induced contraction of opossum sphincter of Oddi. Mechanism of action. Dig Dis Sci. 1990 May;35(5):567–576. doi: 10.1007/BF01540403. [DOI] [PubMed] [Google Scholar]
  12. Hedner P. Effect of the C-terminal octapeptide of cholecystokinin on guinea pig ileum and gall-bladder in vitro. Acta Physiol Scand. 1970 Feb;78(2):232–235. doi: 10.1111/j.1748-1716.1970.tb04658.x. [DOI] [PubMed] [Google Scholar]
  13. Isaza J., Jones D. T., Dragstedt L. R., Woodward E. R. The effect of vagotomy on motor function of the gallbladder. Surgery. 1971 Oct;70(4):616–621. [PubMed] [Google Scholar]
  14. Keast J. R., Furness J. B., Costa M. Distribution of certain peptide-containing nerve fibres and endocrine cells in the gastrointestinal mucosa in five mammalian species. J Comp Neurol. 1985 Jun 15;236(3):403–422. doi: 10.1002/cne.902360308. [DOI] [PubMed] [Google Scholar]
  15. Lotti V. J., Chang R. S. A new potent and selective non-peptide gastrin antagonist and brain cholecystokinin receptor (CCK-B) ligand: L-365,260. Eur J Pharmacol. 1989 Mar 21;162(2):273–280. doi: 10.1016/0014-2999(89)90290-2. [DOI] [PubMed] [Google Scholar]
  16. Marzio L., Di Giammarco A. M., Neri M., Cuccurullo F., Malfertheiner P. Atropine antagonizes cholecystokinin and cerulein-induced gallbladder evacuation in man: a real-time ultrasonographic study. Am J Gastroenterol. 1985 Jan;80(1):1–4. [PubMed] [Google Scholar]
  17. Masclee A. A., Jansen J. B., Driessen W. M., Geuskens L. M., Lamers C. B. Effect of truncal vagotomy on cholecystokinin release, gallbladder contraction, and gallbladder sensitivity to cholecystokinin in humans. Gastroenterology. 1990 May;98(5 Pt 1):1338–1344. doi: 10.1016/0016-5085(90)90354-4. [DOI] [PubMed] [Google Scholar]
  18. Mawe G. M. Intracellular recording from neurones of the guinea-pig gall-bladder. J Physiol. 1990 Oct;429:323–338. doi: 10.1113/jphysiol.1990.sp018259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McLachlan E. M. An analysis of the release of acetylcholine from preganglionic nerve terminals. J Physiol. 1975 Feb;245(2):447–466. doi: 10.1113/jphysiol.1975.sp010855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mo N., Dun N. J. Cholecystokinin octapeptide depolarizes guinea pig inferior mesenteric ganglion cells and facilitates nicotinic transmission. Neurosci Lett. 1986 Mar 14;64(3):263–268. doi: 10.1016/0304-3940(86)90339-3. [DOI] [PubMed] [Google Scholar]
  21. Nemeth P. R., Zafirov D. H., Wood J. D. Effects of cholecystokinin, caerulein and pentagastrin on electrical behavior of myenteric neurons. Eur J Pharmacol. 1985 Oct 22;116(3):263–269. doi: 10.1016/0014-2999(85)90161-x. [DOI] [PubMed] [Google Scholar]
  22. Pellegrini C. A., Lewin M., Patti M. G., Thomas M. J., Ryan T., Way L. W. Gallbladder filling and response to cholecystokinin are not affected by vagotomy. Surgery. 1985 Sep;98(3):452–458. [PubMed] [Google Scholar]
  23. Pendleton R. G., Bendesky R. J., Schaffer L., Nolan T. E., Gould R. J., Clineschmidt B. V. Roles of endogenous cholecystokinin in biliary, pancreatic and gastric function: studies with L-364,718, a specific cholecystokinin receptor antagonist. J Pharmacol Exp Ther. 1987 Apr;241(1):110–116. [PubMed] [Google Scholar]
  24. Pitt H. A., Doty J. E., DenBesten L. Increased intragallbladder pressure response to cholecystokinin-octapeptide following vagotomy and pyloroplasty. J Surg Res. 1983 Oct;35(4):325–331. doi: 10.1016/0022-4804(83)90008-2. [DOI] [PubMed] [Google Scholar]
  25. Shaffer E. A. The effect of vagotomy on gallbladder function and bile composition in man. Ann Surg. 1982 Apr;195(4):413–418. doi: 10.1097/00000658-198204000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tinker J., Cox A. G. Gall-bladder function after vagotomy. Br J Surg. 1969 Oct;56(10):779–782. doi: 10.1002/bjs.1800561022. [DOI] [PubMed] [Google Scholar]
  27. Yau W. M., Makhlouf G. M., Edwards L. E., Farrar J. T. Mode of action of cholecystokinin and related peptides on gallbladder muscle. Gastroenterology. 1973 Sep;65(3):451–456. [PubMed] [Google Scholar]
  28. Zelles T., Harsing L. G., Vizi E. S. Characterization of neuronal cholecystokinin receptor by L-364,718 in Auerbach's plexus. Eur J Pharmacol. 1990 Mar 13;178(1):101–104. doi: 10.1016/0014-2999(90)94799-4. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES