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Effects of Cholecystokinin Receptor Antagonists in Animal Models

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Cholecystokinin Antagonists in Gastroenterology

Abstract

Several peptide and nonpeptide compounds which have recently been described as CCK receptor antagonists in vitro [4–6,17,46] also act as specific antagonists of CCK’s action on exocrine pancreatic secretion of protein and enzymes in vivo. The antagonists display the same rank order of potency in antagonizing CCK’s action on the pancreas in vivo as that which they show in antagonizing CCK’s action and binding in vitro [4–6,17,46] (Fig. 1). However, in particular, the most potent antagonists CR 1409 and L-364718 were 10–33 times less potent in vivo than in vitro. The effects of antagonists on the pancreatic CCK receptor are similar to those recently reported for antagonism of CCK’s action on gastric emptying [17] where a similar difference between in vitro and in vivo potencies had been reported for CR 1409 and L-364718. The reason for the lower in vivo potencies of both peptide and nonpeptide antagonists in relation to their in vitro potencies is unknown. It has been speculated that proglumide (and probably other substances with low in vitro potencies) may be metabolized in vivo to more potent entities [17]. However, very potent antagonists such as CR 1409 or L-364718 may just as well be metabolized in vivo to less active entities.

Dr. Claus Niederau was supported by grants from the Deutsche Forschungsgemeinschaft (Ni 224/1–1, 224/2–1 and 224/2–2) and from the Minister für Wissenschaft und Forschung des Landes Nordrhein-Westfalen. Dr. James H. Grendell was supported by a grant from the National Institute of Health (DK 38939).

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Authors and Affiliations

  1. Medizinische Klinik und Poliklinik, Abteilung für Gastroenterologie, Heinrich-Heine-Universität, 4000, Düsseldorf, Germany

    G. Strohmeyer

  2. Depts. of Medicine, Physiology, and Pathology, University of California, San Francisco, CA, 94143, USA

    J. H. Grendell

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  1. C. Niederau
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  2. M. Niederau
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  3. R. Lüthen
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  4. G. Strohmeyer
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  5. J. H. Grendell
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  1. Abteilung Innere Medizin I, Medizinische Klinik und Poliklinik Oberer Eselsberg, Robert-Koch-Straße 8, W-7900, Ulm, Germany

    Guido Adler

  2. Abteilung für Gastroenterologie, Universitätsklinik, Petersgraben 6, 4031, Basel, Switzerland

    Christoph Beglinger

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Niederau, C., Niederau, M., Lüthen, R., Strohmeyer, G., Grendell, J.H. (1991). Effects of Cholecystokinin Receptor Antagonists in Animal Models. In: Adler, G., Beglinger, C. (eds) Cholecystokinin Antagonists in Gastroenterology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-76362-5_11

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  • DOI: https://doi.org/10.1007/978-3-642-76362-5_11

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