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. 1995 Jun;115(4):660–664. doi: 10.1111/j.1476-5381.1995.tb14983.x

Characterization of the receptors and mechanisms involved in the cardiovascular actions of sCCK-8 in the pithed rat.

A J Gaw 1, D M Hills 1, C F Spraggs 1
PMCID: PMC1908495  PMID: 7582487

Abstract

1. The cardiovascular actions of cholecystokinin and related peptides were investigated in the pithed rat. The receptors and the mechanisms involved in these experiments were characterized. 2. Sulphated cholecystokinin octapeptide (sCCK-8, 0.1-100 nmol kg-1, i.v.) elicited a dose-dependent bradycardia and increase in mean arterial blood pressure. Neither gastrin-17 nor pentagastrin had any effect at concentrations up to 100 nmol kg-1. 3. Both the pressor response and bradycardia elicited by sCCK-8 were reduced by the selective CCKA receptor antagonists, devazepide (0.5-50 nmol kg-1) and lorglumide (1-7 mumol kg-1). The selective CCKB receptor antagonists, CI-988 (1 mumol kg-1) and L-365,260 (15 mumol kg-1) did not inhibit the effects of sCCK-8. 4. The pressor response induced with sCCK-8 was reduced by treatment with either phentolamine (3 mumol kg-1) or guanethidine (2 mumol kg-1) and was unaffected by treatment with propranolol, atropine or hexamethonium. The pressor response also persisted following bilateral adrenalectomy. 5. The bradycardia induced with sCCK-8 was unaffected by treatment with phentolamine, propranolol, guanethidine, atropine, hexamethonium or bilateral adrenalectomy. 6. The tetrapeptide of cholecystokinin (CCK-4) elicited a dose-dependent pressor response but did not induce bradycardia. The pressor response was unaffected by devazepide (50 nmol kg-1), L-365260 (15 mumol kg-1) or phentolamine (3 mumol kg-1). 7. In the pithed rat, sCCK-8 acted via CCKA receptors to increase arterial blood pressure indirectly, at least in part, through activation of alpha-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Bock M. G., DiPardo R. M., Evans B. E., Rittle K. E., Whitter W. L., Veber D. E., Anderson P. S., Freidinger R. M. Benzodiazepine gastrin and brain cholecystokinin receptor ligands: L-365,260. J Med Chem. 1989 Jan;32(1):13–16. doi: 10.1021/jm00121a004. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Hayward N. J., Harding M., Lloyd S. A., McKnight A. T., Hughes J., Woodruff G. N. The effect of CCKB/gastrin antagonists on stimulated gastric acid secretion in the anaesthetized rat. Br J Pharmacol. 1991 Dec;104(4):973–977. doi: 10.1111/j.1476-5381.1991.tb12535.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Hill D. R., Campbell N. J., Shaw T. M., Woodruff G. N. Autoradiographic localization and biochemical characterization of peripheral type CCK receptors in rat CNS using highly selective nonpeptide CCK antagonists. J Neurosci. 1987 Sep;7(9):2967–2976. doi: 10.1523/JNEUROSCI.07-09-02967.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Janssen P. J., Gardiner S. M., Compton A. M., Bennett T. Mechanisms contributing to the differential haemodynamic effects of bombesin and cholecystokinin in conscious, Long Evans rats. Br J Pharmacol. 1991 Jan;102(1):123–134. doi: 10.1111/j.1476-5381.1991.tb12143.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Jensen R. T., Lemp G. F., Gardner J. D. Interactions of COOH-terminal fragments of cholecystokinin with receptors on dispersed acini from guinea pig pancreas. J Biol Chem. 1982 May 25;257(10):5554–5559. [PubMed] [Google Scholar]
  8. 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]
  9. Louie D. S., Liang J. P., Owyang C. Characterization of a new CCK antagonist, L364,718: in vitro and in vivo studies. Am J Physiol. 1988 Sep;255(3 Pt 1):G261–G266. doi: 10.1152/ajpgi.1988.255.3.G261. [DOI] [PubMed] [Google Scholar]
  10. Makovec F., Bani M., Cereda R., Chisté R., Pacini M. A., Revel L., Rovati L. A., Rovati L. C., Setnikar I. Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists. Arzneimittelforschung. 1987 Nov;37(11):1265–1268. [PubMed] [Google Scholar]
  11. Mantyh P. W., Catton M. D., Allen C. J., Labenski M. E., Maggio J. E., Vigna S. R. Receptor binding sites for cholecystokinin, galanin, somatostatin, substance P and vasoactive intestinal polypeptide in sympathetic ganglia. Neuroscience. 1992;46(3):739–754. doi: 10.1016/0306-4522(92)90160-4. [DOI] [PubMed] [Google Scholar]
  12. Marker J. D., Roberts M. L. Chronotropic actions of cholecystokinin octapeptide on the rat heart. Regul Pept. 1988 Mar;20(3):251–259. doi: 10.1016/0167-0115(88)90081-x. [DOI] [PubMed] [Google Scholar]
  13. Moran T. H., Robinson P. H., Goldrich M. S., McHugh P. R. Two brain cholecystokinin receptors: implications for behavioral actions. Brain Res. 1986 Jan 1;362(1):175–179. doi: 10.1016/0006-8993(86)91413-7. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. 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]

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