Exendin-4 and exendin-(9-39)NH2: agonist and antagonist, respectively, at the rat parietal cell receptor for glucagon-like peptide-1-(7-36)NH2
| Autor: | Jens J. Holst, Meinhard Classen, John Eng, Kerstin Dehne, Wolfgang Schepp, Thomas Riedel, Johanna Schmidtler, Volker Schusdziarra, Jean-Pierre Raufman |
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| Rok vydání: | 1994 |
| Předmět: |
endocrine system
medicine.medical_specialty medicine.drug_class Glucagon-Like Peptides Stimulation Peptide In Vitro Techniques complex mixtures Binding Competitive Gastric Acid chemistry.chemical_compound fluids and secretions Parietal Cells Gastric Glucagon-Like Peptide 1 Internal medicine medicine Cyclic AMP Receptors Glucagon Animals Rats Wistar Receptor Aminopyrine Parietal cell Pharmacology chemistry.chemical_classification Venoms digestive oral and skin physiology Cell Membrane Radioimmunoassay Lizards Receptor antagonist Glucagon Adenosine Peptide Fragments Rats medicine.anatomical_structure Endocrinology Cross-Linking Reagents chemistry Exenatide Female Peptides hormones hormone substitutes and hormone antagonists Histamine medicine.drug |
| Zdroj: | European journal of pharmacology. 269(2) |
| ISSN: | 0014-2999 |
| Popis: | Exendin-4 is a novel peptide from Heloderma suspectum venom which is 53% homologous with glucagon-like peptide-1 GLP-1-(7-36)NH2, a stimulant of cAMP-dependent H+ production in rat parietal cells. It was the aim of the present study to determine whether this effect of GLP-1-(7-36)NH2 is shared by exendin-4, and whether the responses to either peptide are blocked by exendin-(9-39)NH2, a competitive specific exendin receptor antagonist. In enriched rat parietal cells H+ production was measured indirectly by [14C]aminopyrine accumulation. cAMP production was determined by radioimmunoassay. [125I]GLP-1-(7-36)NH2 was prepared using chloramine T followed by high pressure liquid chromatography (HPLC) purification. Exendin-4 (10(-12) - 10(-8) M) stimulated [14C]aminopyrine accumulation in a concentration-dependent manner (EC50 = 7.6 x 10(-11) M). At the maximally effective concentration (10(-9) M) exendin-4 was as effective as GLP-1-(7-36)NH2 reaching 70-80% of the response to 10(-4) M histamine. Likewise, exendin-4 (10(-11) - 10(-7) M) stimulated parietal cell cAMP production up to 2.8-fold. Maximal stimulation by exendin-4 of [14C]aminopyrine accumulation was not affected by ranitidine (10(-4) M), but was concentration-dependently reduced by exendin-(9-39)NH2 (10(-11) - 10(-7) M). At the maximal concentration, exendin-(9-39)NH2 completely abolished the responses to 10(-9) M exendin-4 and to 10(-9) M GLP-1-(7-36)NH2 while not altering stimulation by 10(-4) M histamine. Binding of [125I]GLP-1-(7-36)NH2 to enriched parietal cells was displaced by exendin-4 (Ki = 4.6 x 10(-10) M) as well as by exendin-(9-39)NH2 (Ki = 4.0 x 10(-9) M).(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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