1. Activation of Calcitonin Gene-Related Peptide and Adrenomedullin Receptors by PEGylated Adrenomedullin
- Author
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Kazuo Kitamura, Emiko Akashi, Motoo Yamasaki, and Sayaka Nagata
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Pharmaceutical Science ,Peptide ,macromolecular substances ,Calcitonin gene-related peptide ,Receptor Activity-Modifying Protein 2 ,Receptor Activity-Modifying Protein 3 ,Polyethylene Glycols ,Receptor Activity-Modifying Protein 1 ,Adrenomedullin ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Colitis ,Receptor ,Pharmacology ,chemistry.chemical_classification ,Receptor activity-modifying protein ,technology, industry, and agriculture ,General Medicine ,CALCRL ,medicine.disease ,Recombinant Proteins ,HEK293 Cells ,030104 developmental biology ,Endocrinology ,chemistry ,Calcitonin ,030220 oncology & carcinogenesis ,Half-Life - Abstract
Adrenomedullin (AM) improves colitis in animal models and patients with inflammatory bowel disease. We have developed a PEGylated AM derivative (PEG-AM) for clinical application because AM has a short half-life in the blood. However, modification by addition of polyethylene glycol (PEG) may compromise the function of the original peptide. In this paper, we examined the time course of cAMP accumulation induced by 5 and 60 kDa PEG-AM and compared the activation of calcitonin gene-related peptide (CGRP), AM1 and AM2 receptors by AM, 5 and 60 kDa PEG-AM. We also evaluated the effects of antagonists on the action of 5 and 60 kDa PEG-AM. PEG-AM stimulated cAMP production induced by these receptors; the increase in cAMP levels resulting from application of PEG-AM peaked at 15 min. Moreover, PEG-AM activity was antagonized by CGRP (8-37) or AM (22-52) (antagonists of CGRP and AM receptors, respectively) and the maximal response was not suppressed. These findings indicate that the effects of PEG-AM are similar to those of native AM.
- Published
- 2020
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