C-terminal peptides of calcitonin gene-related peptide act as agonists at the cholecystokinin receptor
| Autor: | Tapas K. Pradhan, P.N. Maton, S. Moore |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_specialty Physiology medicine.drug_class Calcitonin Gene-Related Peptide Guinea Pigs Molecular Sequence Data Calcitonin gene-related peptide In Vitro Techniques Biochemistry Cholecystokinin receptor Substance-P Receptor Cellular and Molecular Neuroscience chemistry.chemical_compound Radioligand Assay Endocrinology Internal medicine medicine Cyclic AMP Animals Amylase Amino Acid Sequence Pancreas Cholecystokinin integumentary system biology L-Lactate Dehydrogenase Bombesin Receptor antagonist Peptide Fragments Bombesin receptor nervous system chemistry Amylases biology.protein Calcium Receptors Cholecystokinin |
| Zdroj: | Peptides. 11(6) |
| ISSN: | 0196-9781 |
| Popis: | We have previously described that [Tyr 0 ]CGRP(28–37) acts as a receptor antagonist of rat CGRP in guinea pig pancreatic acini. We therefore examined other C-terminal peptides of CGRP for such activity. CGRP-acetyl(28–37) acetate did act as a rat CGRP antagonist. However, C-terminal CGRP peptides of 4 to 8 amino acid residues did not antagonize the actions of rat CGRP but stimulated amylase secretion. In pancreatic acini, a maximally effective concentration of rat CGRP (100 nM) caused a 2.1-fold increase in amylase secretion. When the C-terminal peptides of CGRP were tested in at 100 μM, CGRP(34–37) caused a 1.8-fold increase in amylase secretion, CGRP(33–37) a 2.8-fold increase, CGRP(32–37) a 9.2-fold increase, CGRP(31–37) a 4.1-fold increase, and CGRP(30–37) a 5.1-fold increase. Further studies with the most effective peptide, CGRP(32–37), demonstrated that it did not cause release of lactate dehydrogenase, and thus did not cause amylase release by cell damage. Unlike rat CGRP, CGRP(32–37) did not increase cellular cyclic AMP, but did stimulate outflux of 45 Ca. CGRP(32–37)-stimulated amylase release was not inhibited by the substance P receptor antagonist, spantide, by the bombesin receptor antagonist, [D-Phe 6 ]bombesin(6–13) propylamide, or by the muscarinic receptor antagonist, atropine, but was inhibited by the CCK receptor antagonist L364,718. C-terminal peptides of CGRP inhibited binding of 125 I-BH-CCK-8, with the relative potencies of the peptides being the same as their relative potencies for stimulating amylase secretion. The present data demonstrate that C-terminal peptides of CGRP, although they have only 2 amino acid residues in common with CCK(26–33), act exclusively at CCK receptors on pancreatic acini to stimulate amylase secretion. |
| Databáze: | OpenAIRE |
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