caa a22 4500 469078987 CHVBK 20180323132944.0 cr unu---uuuuu 170328e19920101xx s 000 0 eng 10.1007/BF00175470 doi (NATIONALLICENCE)springer-10.1007/BF00175470 N-acetyl oxyntomodulin30-37: pharmacokinetics and activity on gastric acid secretion [Elektronische Daten] [Chantal Carles-Bonnet, Claire Jarrousse, Huguette Niel, Jean Martinez, Marc Rolland, Dominique Bataille] Summary: Oxyntomodulin, an intestinal hormone which inhibits gastric acid secretion, is composed of glucagon and a C-terminal octapeptide. This octapeptide mimics the biological activity of the hormone. We have studied the activity of the N-acetyl octapeptide, partially protected against enzymatic degradation, on pentagastrin-, histamine- and milk meal-stimulated secretion in conscious rats and compared it to that of oxyntomodulin and its derivatives. The N-acetylated octapeptide had a 3-fold higher potency than the octapeptide on pentagastrin-stimulated secretion. On histamine-stimulated secretion, the differences between the acetylated and the free octapeptides were that the former displayed a dose-response curve parallel to that of oxyntomodulin and a 4-fold higher potency. The increase in potency appears to be related in part to a decrease in the metabolic clearance rate in vivo (6-fold) and, in vitro, to an increase in half-life (3-fold) when incubated with rat liver plasma membranes. Similarly to the free octapeptide, the acetylated form decreased acid secretion stimulated by a milk meal, when infused before the meal. Acetylation of the Lysine side chains resulted in a totally inactive molecule. The results indicate that acetylating the N-terminus of the octapeptide of oxyntomodulin increases the similarities with the natural hormone. The still large difference in potency (≈ 40-fold) between the 37-amino acid peptide and its acetylated 8-amino acid derivative is explained by the higher (≈ 40-fold) metabolic clearance rate (MCR) of the latter, indicating that further decreasing this parameter, in particular by protecting the short peptide from the enzymatic degradation, should result in a potent and efficient molecule, usable for pharmacological research and therapeutics. Springer-Verlag, 1992 Oxyntomodulin nationallicence Oxyntomodulin30-37 nationallicence Acetylation nationallicence Gastric acid secretion nationallicence Conscious rat nationallicence Carles-Bonnet Chantal Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut Jarrousse Claire Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut Niel Huguette Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut Martinez Jean Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut Rolland Marc Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut Bataille Dominique Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/1(1992-01-01), 57-63 0028-1298 345:1<57 1992 345 210 https://doi.org/10.1007/BF00175470 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00175470 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Carles-Bonnet Chantal Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut NATIONALLICENCE 700 1- Jarrousse Claire Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut NATIONALLICENCE 700 1- Niel Huguette Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut NATIONALLICENCE 700 1- Martinez Jean Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut NATIONALLICENCE 700 1- Rolland Marc Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut NATIONALLICENCE 700 1- Bataille Dominique Centre CNRS-INSEAM de Pharmacologie Endocrinologie, rue de la Cardonille, F-34094, Montpellier Cedex 05, France aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/1(1992-01-01), 57-63 0028-1298 345:1<57 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer