Skip to main content
Log in

Electrophysiological studies of the cholecystokininA receptor antagonists SR27897B and PD140548 in the rat isolated nodose ganglion

  • Short Communication
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

With increased interest in the pharmacology of cholecystokininA (CCKA) receptors, including their trophic and mitogenic effects, the actions of two new non-peptide CCKA receptor antagonists, PD140548 and SR 2789713, were investigated in a convenient model system, the rat isolated nodose ganglion. CCK (1 nM-1 μM) caused concentration-dependent depolarisations when superfused over the nodose ganglion at 37° C as measured by a silicone grease gap technique, and both CCKA antagonists caused significant rightward shifts in the concentration response curve to CCK. SR 2789713 (3 and 10 nM) caused 7.9-and 17.9-fold shifts in the CCK concentration-response curve and the apparent — log KB values for each concentration of antagonist were calculated to be 9.36 and 9.23. Further experiments with PD140548 (30 and 100 nM) yielded shifts of 2.9- and 12.5-fold from which — log KB values were determined to be 7.80 and 8.06. Overall SR 2789713 was significantly more efficacious than PD140548. Thus, the isolated nodose ganglion preparation allows a functional assessment of CCKA-mediated responses, with the results indicating that both SR 27897B and PD 140548 are efficacious CCKA receptor antagonists.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Boden PR, Higginbottom M, Hill DR, Horwell DC, Hughes J, Rees DC, Roberts E, Singh L, Suman-Chauhan N, Woodruff GN (1993) Cholecystokinin dipeptoid antagonists: design, synthesis, and anxiolytic profile of novel CCK-A and CCK-B selective and “mixed” CCK-A/CCK-B antagonists. J Med Chem 36:552–565

    Google Scholar 

  • Carlberg M, Gundlach AL, Mercer LD, Beart PM (1992) Autoradiographic localization of cholecystokinin A and B receptors in rat brain using (125I)D-Tyr25 (N1eu28,31)-CCK 25–33S. Eur J Neurosci 4:563–573

    Google Scholar 

  • Crawley JN, Corwin RL (1994) Biological actions of cholecystokinin. Peptides 15:731–755

    Google Scholar 

  • D'Amato M, Rovati LC (1995) CCK-A antagonists: which and how. Eur J Clin Invest 25:213–214

    Google Scholar 

  • Dockray GJ (1988) Regulatory peptides and the neuroendocrinology of gut-brain relations. Q J Exp Physiol 73:703–727

    Google Scholar 

  • Douglas BR, Woutersen RA, Jansen JBMJ, Jong AJL de, Rovati LC, Lamers CBHW (1989a) Modulation by CR-1409 (lorglumide), a cholecystokinin receptor antagonist, of trypsin-enhanced growth of azaserine-induced putative preneoplastic lesions in rat pancreas. Cancer Res 49:2438–2441

    Google Scholar 

  • Douglas BR, Woutersen RA, Jansen JBMJ, Rovati LC, Lamers CBHW (1989b) Study into the role of cholecystokinin in bombesin-stimulated pancreatic growth in rats and hamsters. Eur J Pharmacol 161:209–214

    Google Scholar 

  • Furchgott (1972) The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Blashko H, Muscholl E (eds) Handbook of experimental pharmacology, vol 33 Springer, Berlin Heidelberg New York, pp 283–335

    Google Scholar 

  • Gallego R, Eyzaguirre C (1978) Membrane and action potential characteristics of A and C nodose ganglion cells studied in whole ganglia and in tissue slices. J Neurophysiol 41:1217–1232

    Google Scholar 

  • Gully D, Fréhel D, Marcy C, Spinazze A, Lespy L, Neliat G, Maffrand J-P, Le Fur G (1993) Peripheral biological activity of SR 27897B: a new potent non-peptide antagonist of CCKA receptors. Eur J Pharmacol 232:13–19

    Google Scholar 

  • Herget T, Sethi T, Wu SV, Walsh JH, Rozengurt E (1994) Cholecystokinin stimulates Ca2+ mobilization and clonal growth in small cell lung cancer through CCKA and CCKB/gastrin receptors. Ann NY Acad Sci 713:283–297

    Google Scholar 

  • Hughes J, Boden P, Costall B, Domeney A, Kelly E, Horwell DC, Hunter JC, Pinnock RD, Woodruff GN (1990) Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc Natl Acad Sci USA 87:6728–6732

    Google Scholar 

  • Innis RB, Snyder SH (1980) Cholecystokinin receptor binding in brain and pancreas: regulation of pancreatic binding by cyclic nucleotides. Eur J Pharmacol 65:123–124

    Google Scholar 

  • Lamers CBHW, Jansen JBMJ, Woutersen RA (1990) Cholecystokinin and gastrointestinal cancer. J Steroid Biochem Molec Biol 37:1069–1072

    Google Scholar 

  • Lentner C (1982) Documenta Geigy Scientific Tables. 8th ed, Ciba Geigy, Basel, pp 210–215

    Google Scholar 

  • Mei N (1985) Intestinal chemosensitivity. Physiol Rev 65:211–237

    Google Scholar 

  • Meyer BM, Beglinger C, Jansen JBM, Rovati LC, Werth BA, Hildebrand P, Zach D, Stadler GA (1989) Role of cholecystokinin in regulation of gastrointestinal motor function. Lancet II:12–15

    Google Scholar 

  • Raybould HE, Tache Y (1988) Cholecystokinin inhibits gastric motility and emptying via a capsaicin-sensitive vagal pathway in rats. Am J Physiol 255:G242-G246

    Google Scholar 

  • Walsh JH (1987) Gastrointestinal hormones: cholecystokinin. In: Johnson LR, Christensen J, Jackson MJ, Jacobson ED, Walsh JH (eds) Physiology of the gastrointestinal tract, 2 edn. Raven Press, New York, pp 181–253

    Google Scholar 

  • Wank SA, Pisegna JR, De Weerth A (1994) Cholecystokinin receptor family. Molecular cloning, structure, and functional expression in rat, guinea pig, and human. Ann NY Acad Sci 713:49–66

    Google Scholar 

  • Widdop RE, Krstew E, Jarrott B (1990) Temperature dependence of angiotensin II-mediated depolarisation of the rat isolated nodose ganglion. Eur J Pharmacol 185:107–111

    Google Scholar 

  • Widdop RE, Krstew E, Mercer LD, Carlberg M, Beart PM, Jarrott B (1993) Electrophysiological and autoradiographic evidence for cholecystokinin A receptors on rat isolated nodose ganglia. J Autonom Nerv System 46:65–73

    Google Scholar 

  • Woll PJ, Rozengurt E (1989) Multiple neuropeptides mobilise calcium in small lung cell cancer: effects of vasopressin, bradykinin, cholecystokinin, galanin and neurotensin. Biochem Biophys Res Commun 164:66–73

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beart, P.M., Krstew, E. & Widdop, R.E. Electrophysiological studies of the cholecystokininA receptor antagonists SR27897B and PD140548 in the rat isolated nodose ganglion. Naunyn-Schmiedeberg's Arch Pharmacol 353, 693–697 (1996). https://doi.org/10.1007/BF00167190

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00167190

Key words

Navigation