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. 1993 Aug;109(4):913–917. doi: 10.1111/j.1476-5381.1993.tb13707.x

Characterization of CCK receptors in a novel smooth muscle preparation from the guinea-pig stomach by use of the selective antagonists CI-988, L-365,260 and devazepide.

S J Boyle 1, K W Tang 1, G N Woodruff 1, A T McKnight 1
PMCID: PMC2175762  PMID: 8401944

Abstract

1. The cholecystokinin receptors mediating motor responses in a novel smooth muscle preparation from the corpus region of the guinea-pig stomach have been characterized by use of five agonist peptides and the antagonists CI-988, L-365,260 and devazepide. 2. Mucosa-denuded strips of circular muscle were contracted in a concentration-dependent manner by the five cholecystokinin (CCK)-related peptides CCK-8S, pentagastrin, gastrin-I, CCK-8US and CCK-4. 3. CI-988 was a powerful antagonist of the response to pentagastrin with an affinity (pKB = 9.49) similar to that obtained in CCKB receptor binding assays. With CCK-8S as the agonist, CI-988 was approximately 1000 fold less powerful as an antagonist. 4. Devazepide powerfully blocked responses to CCK-8S with an affinity (pKB = 9.54) that was in agreement with reported functional data obtained in pancreatic amylase secretion studies, a system exhibiting CCKA receptor activity. Devazepide displayed lower affinity against pentagastrin than against CCK-8S. 5. CI-988 blocked responses to pentagastrin in an insurmountable manner in the presence of 3 nM devazepide; a concentration previously shown to block the CCKA receptor. The nature of the antagonism observed with L-365,260 was unaltered by the presence of devazepide. 6. The guinea-pig stomach corpus smooth muscle preparation contains both subtypes of CCK receptor and will be useful as a pharmacological tool for investigating the functional effects of novel CCK ligands.

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bitar K. N., Makhlouf G. M. Receptors on smooth muscle cells: characterization by contraction and specific antagonists. Am J Physiol. 1982 Apr;242(4):G400–G407. doi: 10.1152/ajpgi.1982.242.4.G400. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Cherner J. A., Sutliff V. E., Grybowski D. M., Jensen R. T., Gardner J. D. Functionally distinct receptors for cholecystokinin and gastrin on dispersed chief cells from guinea pig stomach. Am J Physiol. 1988 Feb;254(2 Pt 1):G151–G155. doi: 10.1152/ajpgi.1988.254.2.G151. [DOI] [PubMed] [Google Scholar]
  5. Collins S. M., Gardner J. D. Cholecystokinin-induced contraction of dispersed smooth muscle cells. Am J Physiol. 1982 Dec;243(6):G497–G504. doi: 10.1152/ajpgi.1982.243.6.G497. [DOI] [PubMed] [Google Scholar]
  6. Eckman D. M., Frankovich J. D., Keef K. D. Comparison of the actions of acetylcholine and BRL 38227 in the guinea-pig coronary artery. Br J Pharmacol. 1992 May;106(1):9–16. doi: 10.1111/j.1476-5381.1992.tb14285.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Freidinger R. M. Non-peptide ligands for peptide receptors. Trends Pharmacol Sci. 1989 Jul;10(7):270–274. doi: 10.1016/0165-6147(89)90026-6. [DOI] [PubMed] [Google Scholar]
  8. Grider J. R., Makhlouf G. M. Distinct receptors for cholecystokinin and gastrin on muscle cells of stomach and gallbladder. Am J Physiol. 1990 Aug;259(2 Pt 1):G184–G190. doi: 10.1152/ajpgi.1990.259.2.G184. [DOI] [PubMed] [Google Scholar]
  9. Grider J. R., Makhlouf G. M. Regional and cellular heterogeneity of cholecystokinin receptors mediating muscle contraction in the gut. Gastroenterology. 1987 Jan;92(1):175–180. doi: 10.1016/0016-5085(87)90855-9. [DOI] [PubMed] [Google Scholar]
  10. Hill D. R., Shaw T. M., Woodruff G. N. Species differences in the localization of 'peripheral' type cholecystokinin receptors in rodent brain. Neurosci Lett. 1987 Aug 31;79(3):286–289. doi: 10.1016/0304-3940(87)90445-9. [DOI] [PubMed] [Google Scholar]
  11. Huang S. C., Zhang L., Chiang H. C., Wank S. A., Maton P. N., Gardner J. D., Jensen R. T. Benzodiazepine analogues L365,260 and L364,718 as gastrin and pancreatic CCK receptor antagonists. Am J Physiol. 1989 Jul;257(1 Pt 1):G169–G174. doi: 10.1152/ajpgi.1989.257.1.G169. [DOI] [PubMed] [Google Scholar]
  12. Hughes J., Boden P., Costall B., Domeney A., Kelly E., Horwell D. C., Hunter J. C., Pinnock R. D., Woodruff G. N. Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6728–6732. doi: 10.1073/pnas.87.17.6728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Innis R. B., Snyder S. H. Distinct cholecystokinin receptors in brain and pancreas. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6917–6921. doi: 10.1073/pnas.77.11.6917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knapp R. J., Vaughn L. K., Fang S. N., Bogert C. L., Yamamura M. S., Hruby V. J., Yamamura H. I. A new, highly selective CCK-B receptor radioligand ([3H][N-methyl-Nle28,31]CCK26-33): evidence for CCK-B receptor heterogeneity. J Pharmacol Exp Ther. 1990 Dec;255(3):1278–1286. [PubMed] [Google Scholar]
  15. Kondo K., Mitchell J. A., de Nucci G., Vane J. R. Simultaneous measurement of endothelium-derived relaxing factor by bioassay and guanylate cyclase stimulation. Br J Pharmacol. 1989 Oct;98(2):630–636. doi: 10.1111/j.1476-5381.1989.tb12637.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Lucaites V. L., Mendelsohn L. G., Mason N. R., Cohen M. L. CCK-8, CCK-4 and gastrin-induced contractions in guinea pig ileum: evidence for differential release of acetylcholine and substance P by CCK-A and CCK-B receptors. J Pharmacol Exp Ther. 1991 Feb;256(2):695–703. [PubMed] [Google Scholar]
  18. Margolis R. L., Moran T. H., McHugh P. R. In vitro response of rat gastrointestinal segments to cholecystokinin and bombesin. Peptides. 1989 Jan-Feb;10(1):157–161. doi: 10.1016/0196-9781(89)90092-2. [DOI] [PubMed] [Google Scholar]
  19. Meldrum L. A., Bojarski J. C., Calam J. Effects of benzodiazepines on responses of guinea-pig ileum and gall-bladder and rat pancreatic acini to cholecystokinin. Eur J Pharmacol. 1986 Apr 29;123(3):427–432. doi: 10.1016/0014-2999(86)90719-3. [DOI] [PubMed] [Google Scholar]
  20. Patel M., Spraggs C. F. Functional comparisons of gastrin/cholecystokinin receptors in isolated preparations of gastric mucosa and ileum. Br J Pharmacol. 1992 Jun;106(2):275–282. doi: 10.1111/j.1476-5381.1992.tb14328.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rehfeld J. F. Four basic characteristics of the gastrin-cholecystokinin system. Am J Physiol. 1981 Apr;240(4):G255–G266. doi: 10.1152/ajpgi.1981.240.4.G255. [DOI] [PubMed] [Google Scholar]
  22. Stretton C. D., Barnes P. J. Cholecystokinin-octapeptide constricts guinea-pig and human airways. Br J Pharmacol. 1989 Jul;97(3):675–682. doi: 10.1111/j.1476-5381.1989.tb12003.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Woodruff G. N., Hill D. R., Boden P., Pinnock R., Singh L., Hughes J. Functional role of brain CCK receptors. Neuropeptides. 1991 Jul;19 (Suppl):45–56. doi: 10.1016/0143-4179(91)90082-t. [DOI] [PubMed] [Google Scholar]
  24. Woodruff G. N., Hughes J. Cholecystokinin antagonists. Annu Rev Pharmacol Toxicol. 1991;31:469–501. doi: 10.1146/annurev.pa.31.040191.002345. [DOI] [PubMed] [Google Scholar]
  25. Zetler G. Ceruletide, ceruletide analogues and cholecystokinin octapeptide (CCK-8): effects on isolated intestinal preparations and gallbladders of guinea pigs and mice. Peptides. 1984 Jul-Aug;5(4):729–736. doi: 10.1016/0196-9781(84)90014-7. [DOI] [PubMed] [Google Scholar]

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