Partial agonism by gastrin for a cholecystokinin receptor mediating pepsinogen secretion
| Autor: | L. H. Tang, M. D. Miller, James R. Goldenring, I. M. Modlin, S. J. Hersey |
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| Rok vydání: | 1993 |
| Předmět: |
Agonist
medicine.medical_specialty Physiology medicine.drug_class Molecular Sequence Data In Vitro Techniques Biology Devazepide digestive system Partial agonist Cholecystokinin receptor Sincalide chemistry.chemical_compound Physiology (medical) Internal medicine Gastric glands Gastrins medicine Animals Amino Acid Sequence Receptor Gastrin Cholecystokinin Benzodiazepinones Pepsinogens Sequence Homology Amino Acid Hepatology Cell Membrane digestive oral and skin physiology Gastroenterology Asperlicin Hormones Kinetics Endocrinology medicine.anatomical_structure chemistry Gastric Mucosa Receptors Cholecystokinin Rabbits Oligopeptides hormones hormone substitutes and hormone antagonists |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 265:G865-G872 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.1993.265.5.g865 |
| Popis: | Isolated gastric glands from rabbit were used to characterize the functional cholecystokinin (CCK)-like peptide receptors that mediate pepsinogen secretion. Pepsinogen secretion was stimulated by both CCK octapeptide sulfate (CCK-8) and A-71378, a selective CCK-A-type receptor agonist, with similar mean effective doses (1.0 and 0.8 nM, respectively). Compared with CCK-8, gastrin-17 (G-17-I) showed reduced potency and only partial efficacy for stimulation of pepsinogen secretion while inhibiting the maximal CCK-8-stimulated response. The nonpeptide inhibitors, asperlicin and L-364,718, inhibited pepsinogen secretion with identical pA2 values for antagonism of both CCK and gastrin, indicating that both peptides interact with the same functional receptor. Specific binding of [3H]CCK-8 to isolated chief cell membranes was displaced fully by both CCK and gastrin, indicating full receptor occupancy by both peptides. A novel synthetic peptide analogue, pseudogastrin [(Glu)5-Ala-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2], was used to investigate the structural basis for the lower potency and efficacy of G-17-I. The potency of CCK and gastrin analogues for pepsinogen secretion was found to be dependent on both sulfation of a tyrosine residue and the position of the tyrosine residue relative to the COOH-terminal phenylalanine amide. The efficacy appears to be determined partially by the extended NH2-terminal sequence of G-17-I. The results of the present study are interpreted to show that pepsinogen secretion is mediated by a CCK-A-type receptor and gastrin acts at the same receptor as a partial agonist. |
| Databáze: | OpenAIRE |
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